Skip to main content

Advertisement

Log in

Local renin–angiotensin systems in the genitourinary tract

  • Review
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Local renin–angiotensin systems are common throughout the human body. Recent evidence supports the existence of such local renin–angiotensin systems in the penis, clitoris, bladder, ureter, internal anal sphincter, and urethral sphincter. Beyond its role in regulating blood pressure through its effects on vascular tone, sodium balance, and fluid homeostasis, angiotensin II serves a key role in affecting physiologic and pathophysiologic activities of the genitourinary tract. Just as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are used for the treatment and prevention of heart disease and vascular disease, inhibition of excessive angiotensin II activity may be potentially useful for the treatment of urologic disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Abadir PM, Periasamy A, Carey RM, Siragy HM (2006) Angiotensin II type 2 receptor-bradykinin B2 receptor functional heterodimerization. Hypertension 48:316–322

    Article  PubMed  CAS  Google Scholar 

  • Anderson KE, Persson K (1995) Nitric oxide synthase and the lower urinary tract: possible implication for physiology and pathophysiology. Scand J Urol Nephrol 29:43–53

    Google Scholar 

  • Andersson K-E (2003) Erectile physiological and pathophysiological pathways involved in erectile dysfunction. J Urol 170:S6–S14

    Article  PubMed  Google Scholar 

  • Andersson KE, Hedlund H, Stahl M (1992) Contractions induced by angiotensin I, angiotensin II, and bradykinin in isolated muscle from the human detrusor. Acta Physiol Scand 145:253–259

    Article  PubMed  CAS  Google Scholar 

  • Ardaillo R, Chansel D (1997) Synthesis and effects of active fragments of angiotensin II. Kidney Int 52:1458–1468

    Article  Google Scholar 

  • Ayan S, Roth JA, Freeman MR, Bride SH, Peters CA (2001) Partial ureteral obstruction dysregulates the renal renin-angiotensin system in the fetal sheep kidney. Urology 58:301–306

    Article  PubMed  CAS  Google Scholar 

  • Azadzoi KM, Keim VK, Tarcan T, Siroky MB (2004) Alteration of urothelial-mediated tone in the ischemic bladder: role of eicosanoids. Neurourol Urodyn 23:258–264

    Article  PubMed  CAS  Google Scholar 

  • Bader M, Ganten D (2008) Update on tissue renin–angiotensin systems. J Mol Med 86:615–621

    Article  PubMed  CAS  Google Scholar 

  • Batenburg WW, Garrelds IM, Bernasonic CC et al (2004) Angiotensin II type 2 receptor-mediated vasodilation in human coronary microareteries. Circulation 109:2296–2301

    Article  PubMed  CAS  Google Scholar 

  • Becker AJ, Uckert S, Stief CG et al (2001a) Plasma levels of angiotensin II during different penile conditions in the cavernous and systemic blood of healthy men and patients with erectile dysfunction. Urology 58:805–810

    Article  PubMed  CAS  Google Scholar 

  • Becker AJ, Ückert S, Stief CG, Truss MC, Machtens S, Scheller F, Knapp WH, Hartmann U, Jonas U (2001b) Possible role of bradykinin and angiotensin II in the regulation of penile erection and detumescence. Urology 57:193–198

    Article  PubMed  CAS  Google Scholar 

  • Boivin D, Bilodeau D, Beliveau R (1996) Regulation of cytoskeletal functions by Rho small GTP-binding proteins in normal and cancer cells. Can J Physiol Pharmacol 74:801–810

    Article  PubMed  CAS  Google Scholar 

  • Border WA, Noble NA (1998) Interactions of transforming growth factor-beta and angiotensin II in renal fibrosis. Hypertension 31:181–188

    PubMed  CAS  Google Scholar 

  • Brasch H, Sieroslawski L, Dominiak P (1993) Angiotensin II increases norepinephrine release from atria by acting on angiotensin subtype 1 receptors. Hypertension 22:699–704

    PubMed  CAS  Google Scholar 

  • Brilla CG, Reams GP, Maisch B, Weber KT (1993) Renin angiotensin system and myocardial fibrosis in hypertension: regulation of the myocardial collagen matrix. Eur Heart J 14:S57–S61

    Article  Google Scholar 

  • Bullock AD, Becich MJ, Klutke CG, Ratliff TL (1992) Experimental autoimmune cystitis: a potential murine model for ulcerative interstitial cystitis. J Urol 148:1951–1956

    PubMed  CAS  Google Scholar 

  • Burnett AL (1997) Nitric oxide in the penis: physiology and pathology. J Urol 157:320–324

    Article  PubMed  CAS  Google Scholar 

  • Burnett AL, Msicki B, Jin L, Bivalacqua TJ (2006) Nitric oxide/redox-based signaling as a therapeutic target for penile disorders. Expert Opin Ther Targets 10:445–457

    Article  PubMed  CAS  Google Scholar 

  • Butkus A, Albiston A, Alcorn D et al (1997) Ontogeny of angiotensin II receptors, types 1 and 2, in ovine mesonephros and metanephros. Kidney Int 51:628–636

    Article  Google Scholar 

  • Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular disease: the role of oxidative stress. Circ Res 87:840–844

    PubMed  CAS  Google Scholar 

  • Carey RM, Siragy HM (2003) Newly recognized components of the renin-angiotensin system: potential roles in cardiovascular and renal regulation. Endocr Rev 24:261–271

    Article  PubMed  CAS  Google Scholar 

  • Celik AF, Katsinelos P, Read NW, Khan MI, Donnelly TC (1995) Hereditary proctalgia fugax and constipation: report of a second family. Gut 36:581–584

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Li SX, Yao LS, Wang R, Dai YT (2006) Valsartan treatment reverses erectile dysfunction in diabetic rats. Int J Impot Res 19:366–370

    Article  PubMed  CAS  Google Scholar 

  • Cheng EY, Grammatopoulos T, Lee C, Decker R, Sensibar J, Kaplan WE, Maizels M, Firlit CF (1996) Angiotensin II and basic fibroblast growth factor induce neonatal bladder stromal cell mitogenesis. J Urol 156:593–597

    Article  PubMed  CAS  Google Scholar 

  • Cheng EY, Chung L, Decker RS et al (1997) Captopril (an inhibitor of angiotensin converging enzyme) inhibits obstructive changes in the neonatal rabbit bladder. Urology 50:465–471

    Article  PubMed  CAS  Google Scholar 

  • Chicurel ME, Chen CS, Ingber DE (1998) Cellular control lies in the balance of forces. Curr Opin Cell Biol 10:232–239

    Article  PubMed  CAS  Google Scholar 

  • Cohn JN (2006) What is the role of angiotensin-receptor blockade in cardiovascular protection? Am Heart J 152(859):e.1–e.8

    Google Scholar 

  • Comiter CV, Phull HS (2011) Angiotensin II type 1 (AT1) receptor inhibition prevents the urodynamic and detrusor changes associated with bladder outlet obstruction—a mouse model. BJU Int. doi:10.1111/j.1464-410X.2011.10580.x

  • Comiter CV, Sullivan MP, Yalla SV et al (1997) Effect of angiotensin II on corpus cavernosum smooth muscle in relation to nitric oxide environment: in vitro studies in canines. Int J Impot Res 9:135–140

    Article  PubMed  CAS  Google Scholar 

  • Cooper GLV, Mercer WE, Hoober JK et al (1986) Load regulation of the properties of adult feline cardiocytes. The role of substrate adhesion. Circ Res 58:692–705

    PubMed  Google Scholar 

  • Cruzado MC, Risler NR, Miatello RM et al (2005) Vasclar smooth muscle cell SNDPH activity during the development of hypertension: effect of angiotensin II and role of inslinlike growth factor-1 receptor transactivation. Am J Hypertens 18:81–87

    Article  PubMed  CAS  Google Scholar 

  • Darby IA, Congiu M, Fernley RT (1994) Cellular and ultrastructural location of antiotensinogen in rat and sheep kidney. Kidney Int 46:1557–1560

    Article  PubMed  CAS  Google Scholar 

  • de Gasparo M (2002) Angiotensin II and nitric oxide interaction. Heart Fail Rev 7:347–358

    Article  PubMed  Google Scholar 

  • De Godoy MAF, Rattan S (2005) Autocrine regulation if internal anal sphincter tone by renin-angiotensin system: comparison with phasic smooth muscle. Am J Physiol 289:G1164–G1175

    Google Scholar 

  • De Godoy MAF, Rattan S (2006) Angiotensin-converting enzyme and angiotensin II receptor subtype 1 inhibitors restitute hypertensive internal anal sphincter in the spontaneously hypertensive rats. JPET 318:725–734

    Article  CAS  Google Scholar 

  • De Godoy MAF, de Oliveira AM, Rattan S (2004) Angiotensin II-induced relaxation of anococcygeus smooth muscle via desensitization of AT1 receptor, and activation of At2 receptor associated with nitric-oxide synthase pathway. JPET 311:394–401

    Article  CAS  Google Scholar 

  • Dorrance AM, Lewis RW, Mills TM (2002) Captopril treatment reverses erectile dysfunction in male stroke prone spontaneously hypertensive rats. Int J Impot Res 14:494–497

    Article  PubMed  CAS  Google Scholar 

  • Dzau VJ, Pratt RE (1993) Cardiac, vascular and intrarenal rennin angiotensin system in normal physiology and disease. In: Robertson JIS, Nicholls MG (eds) The renin–angiotensin system. Gower, London, pp 1–11

    Google Scholar 

  • Dzielak DJ (1992) The immune system and hypertension. Hypertension 19(Suppl):I36–I44

    PubMed  CAS  Google Scholar 

  • El Dahr SS, Gee J, Dipp S et al (1993) Upregulation of renin-angiotensin system and downregulation of kallikrein in obstructive nephropathy. Am J Physiol 264:F874–F881

    PubMed  CAS  Google Scholar 

  • El Melegy NT, Ali ME, Awad EM (2005) Plasma levels of endothelin-1, angiotensin II, nitric oxide and prostaglandin E in the venous and cavernosal blood of patients with erectile dysfunction. BJU Int 96:1079–1086

    Article  PubMed  CAS  Google Scholar 

  • Esther CR Jr, Howard TE, Marino EM, Goddard JM, Capecchi MR, Bernstein KE (1996) Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility. Lab Invest 7:953–965

    Google Scholar 

  • Fan Y-P, Pri RN, Rattan S (2002) Animal model for angiotensin II effects in the internal anal sphincter smooth muscle: mechanism of action. Am J Physiol 282:G462–G469

    Google Scholar 

  • Fern RJ, Vesko CM, Thornhill BA et al (1999) Reduced angiotensinogen expression attenuates renal interstitial fibrosis in obstructive nephropathy in mice. J Clin Invest 103:39–46

    Article  PubMed  CAS  Google Scholar 

  • Freeman EJ, Tallant EA (1994) Vasclar smooth-muscle cells contain AT1 angiotensin receptors coupled to phospholipase D activation. Biochem J 304:543–548

    PubMed  CAS  Google Scholar 

  • Fujinaka H, Miyazaki Y, Matsusaka T, Yoshida H, Fogo AB, Inagami T et al (2000) Salutary role for angiotensin in partial urinary tract obstruction. Kidney Int 58:2018–2017

    Article  PubMed  CAS  Google Scholar 

  • Gase JM, Shanmugam S, Sibony M, Corvol P (1994) Tissue-specific expression of type 1 angiotensin II receptor subtypes. An in situ hybridization study. Hypertension 24:531–537

    Google Scholar 

  • Gilmom RF, Khoury AE, Macarak EJ, McLorie GA, Steckler RE, Kogan BA (1994) Loss of elasticity in dysfunctional bladders: urodynamic and histochemical correlation. J Urol 152:702–705

    Google Scholar 

  • Gobet R, Park JM, Nguyen HT et al (1999) Renal renin-angiotensin system dysregulation casued by partial bladder outlet obstruction in fetal sheep. Kidney Int 56:1654–1661

    Article  PubMed  CAS  Google Scholar 

  • Goldstein I, Berman JR (1998) Vasculogenic female sexal dysfnction: vaginal engorgement and clitoral erectile insufficiency syndromes. Int J Impot Res 10:S84–S90

    PubMed  Google Scholar 

  • Greenland JE, Brading AF (1997) The in vivo and in vitro effects of hypoxia on pig urethral smooth muscle. BJU Int 79:525–531

    Article  CAS  Google Scholar 

  • Greenland JE, Hvistendahl JJ, Andersen H et al (2000) The effect of bladder outlet obstruction on tissue oxygen tension and blood flow in the pig bladder. BJU Int 85:1109–1114

    Article  PubMed  CAS  Google Scholar 

  • Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK et al (2006) Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 312:117–121

    Article  PubMed  CAS  Google Scholar 

  • Hansson L, Lindholm LH, Ekbom T et al (1999a) Randomized trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 Study. Lancet 354:1751–1756

    Article  PubMed  CAS  Google Scholar 

  • Hansson L, Lindholm LH, Niskanen L et al (1999b) Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomized trial. Lancet 353:611–616

    Article  PubMed  CAS  Google Scholar 

  • Holmquist F, Persson K, Garcia-Pascual A et al (1992) Phospholipase C activation by endothelin-1 and noradrenaline in isolated penile erectile tissue from rabbit. J Urol 147:1632–1635

    PubMed  CAS  Google Scholar 

  • Ishidoya S, Morrissey J, McCracken R, Reyes A, Klahr S (1995) Angiotensin II receptor antagonist ameliorates renal tubulointerstitial fibrosis caused by unilateral ureteral obstruction. Kidney Int 47:1285–1294

    Article  PubMed  CAS  Google Scholar 

  • Ishidoya S, Morrissey J, McCracken R, Klahr S (1996) Delayed treatment with enalapril halts tubulointerstitial fibrosis in rats with obstructive nephropathy. Kidney Int 49:1110–1119

    Article  PubMed  CAS  Google Scholar 

  • Iwamoto Y, Song K, Takai S et al (2001) Multiple pathways of angiotensin I conversion and their functional role in the canine penile corpus cavernosum. J Pharmacol Exp Ther 298:43–48

    PubMed  CAS  Google Scholar 

  • Jin L-M (2009) Angiotensin II signaling and its implication in erectile dysfunction. J Sex Med 6(suppl 3):302–210

    Article  PubMed  CAS  Google Scholar 

  • Jin L, Ying Z, Webb RC (2004) Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta. Am J Physiol Heart Circ Physiol 287:H1495–H1500

    Article  PubMed  CAS  Google Scholar 

  • Jin L, Ying Z, Hilgers RH et al (2006) Increased Rhoa/Rho-kinase signaling mediates spontaneous tone in aorta from angiotensin II-induced hypertensive rats. J Pharmacol Exp Ther 318:288–295

    Article  PubMed  CAS  Google Scholar 

  • Jin L, Lagoda G, Leite R, Webb RC, Burnett AL (2008) NADPH oxidase activation: a mechanism of hypertension-associated erectile dysfunction. J Sex Med 5:544–551

    Article  PubMed  CAS  Google Scholar 

  • Kaneto H, Morrissey J, McCracken R, Reyes A, Klahr S (1994) Enalapril reduces collagen type IV synthesis and expansion of the interstitium in the obstructed rat kidney. Kidney Int 45:1637–1647

    Article  PubMed  CAS  Google Scholar 

  • Kato K, Monson F, Longhurst P, Wein A, Haugaard N, Levin R (1990) The functional effects of long-term outlet obstruction on the rabbit urinary bladder. J Urol 143:600–606

    PubMed  CAS  Google Scholar 

  • Kato H, Suzuki H, Tajima S, Ogata Y, Tominaga T, Sato A, Saruta T (1991) Angiotensin II stimulates collagen synthesis in cultured vascular smooth muscle cells. J Hypertens 9:17–22

    PubMed  CAS  Google Scholar 

  • Kawazoe T, Kosaka H, Yoneyama H et al (2000) Acute production of vascular speroxide by Ang-II but not by catecholamines. J Hypertens 18:179–185

    Article  PubMed  CAS  Google Scholar 

  • Kifor I, Williams G, Vickers M et al (1997) Tissue angiotensin II as a modulator of erectile function. 1. Angiotensin peptide content, secretion and effects in the corpus cavernosum. J Urol 157:1920–1925

    Article  PubMed  CAS  Google Scholar 

  • Kim KM, Kogan BA, Massad CA, Huang YC (1991) Collagen and elastin in the obstructed fetal bladder. J Urol 146:528–531

    PubMed  CAS  Google Scholar 

  • Klahr S, Morrissey JJ (1997) Comparative study of ACE inhibitors and angiotensin II receptor antagonists in interstitial scarring. Kidney Int 52:S111–S114

    Article  Google Scholar 

  • Klett CP, Printz MP, Bader M, Ganten D, Eggena P (1996) Angiotensinogen messenger RNA stabilization by angiotensin II. J Hypertens Suppl 14:S25–S36

    PubMed  CAS  Google Scholar 

  • Lam DSH, Dias LS, Moore KH et al (2000) Angiotensin II in child urinary bladder: functional and autoradiographic studies. Br J Urol 86:494–501

    Article  CAS  Google Scholar 

  • Lee VC, Rhew DC, Dylan M et al (2004) Meta-analysis: angiotensin-receptor blockers in chronic heart failure and high-risk acute myocardial infarction. Ann Intern Med 141:693–704

    PubMed  CAS  Google Scholar 

  • Leiblum SR, Bame RM, Croog SH (1994) The sexual functioning of elderly hypertensive women. J Sex Marital Ther 20:250–270

    Article  Google Scholar 

  • Lindberg BF, Nillson LG, Hedlund H, Stahl M, Andersson KE (1994) Angiotensin I is converted to angiotensin II by a serine protease in human detrusor smooth muscle. Am J Physiol 266:R1861–R1867

    PubMed  CAS  Google Scholar 

  • Lithell H, Hansson L, Skoog I et al (2003) The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 21:875–886

    Article  PubMed  CAS  Google Scholar 

  • Lonn EM, Yusuf S, Jha P et al (1994) Emerging role of angiotensin-converting enzyme inhibitors in cardiac and vascular protection. Circulation 90:2056–2069

    PubMed  CAS  Google Scholar 

  • Ma J, Fogo NH, Inagami KV et al (1998) Accelerated fibrosis and collagen deposition develop in the renal interstitium of angiotensin type 2 receptor null mutant mice during ureteral obstruction. Kidney Int 53:937–944

    Article  PubMed  CAS  Google Scholar 

  • Mann DL, Kent RL, Cooper G (1989) Load regulation of the properties of adult feline cardiocytes: growth induction by cellular deformation. Circ Res 64:1079–1090

    PubMed  CAS  Google Scholar 

  • Mazza ON, Angerosa M, Becher E, Toblli JE (2006) Differences between Candesartan and Hydralazine in the protection of penile structures in spontaneously hypertensive rats. J Sex Med 3:604–611

    Article  PubMed  CAS  Google Scholar 

  • Mikata N, Iwai N, Inagami T et al (1992) Two distinct pathways in the downregulation of type 1 angiotensin receptor gene in rat glomerular mesangial cells. Biochem Biophy Res Commun 185:142–146

    Article  Google Scholar 

  • Millan MA, Jacobowitz DM, Aguilera G, Catt KJ (1991) Differential distribution of AT1 and AT2 angiotensin II receptor subtypes in the rat brain during development. Proc Natl Acad Sci U S A 88:11440–11444

    Article  PubMed  CAS  Google Scholar 

  • Mills TM, Chitaley K, Lewis RW, Webb RC (2002) Nitric oxide inhibits RhoA/Rho-kinase signaling to case penile erection. Eur J Pharmacol 439:173–174

    Article  PubMed  CAS  Google Scholar 

  • Miyazaki Y, Tsuchida S, Nishimura H et al (1998) Angiotensin induces the urinary peristaltic machinery during the perinatal period. J Clin Invest 102:1489–1497

    Article  PubMed  CAS  Google Scholar 

  • Mizuno K, Tani M, Hashimoto S et al (1992) Effects of losartan, a nonpeptide angiotensin II receptor antagonist, on cardiac hypertrophy and the tissue angiotensin II content in spontaneously hypertensive rats. Life Sci 51:367–374

    Article  PubMed  CAS  Google Scholar 

  • Morrissey JJ, Klahr S (1997) Enalapril decreases nuclear factor kappa B activation in the kidney with ureteral obstruction. Kidney Int 52:926–933

    Article  PubMed  CAS  Google Scholar 

  • Mukoyama M, Nakajima M, Horiuchi M et al (1993) Expression cloning of type 2 angiotensin II receptor reveals a unique class of seven-transmembrane receptors. J Biol Chem 268:24539–24542

    PubMed  CAS  Google Scholar 

  • Nagata M, Tanimoto K, Fukamizu A, Kon Y, Sugiyama F, Yagami K, Murakami K, Watanabe T (1996) Nephrogenesis and renovascular development in angiotensinogen-deficient mice. Lab Invest 75:745–753

    PubMed  CAS  Google Scholar 

  • Nakasawa R, Tanaka M, Takahashi T et al (2007) Effects of castration and testosterone administration on angiotensin II receptor mRNA expression and apoptosis-related proteins in rat urinary bladder. Endocr J 54:211–219

    Article  Google Scholar 

  • Nakashima H, Suzuki H, Ohtsu H et al (2006) Angiotensin II regulates vascular and endothelial dysfunction: recent topics of angiotensin Ii type-1 signaling in the vasculature. Curr Vasc Pharmacol 4:67–78

    Article  PubMed  CAS  Google Scholar 

  • Navar LG, Inscho EW, Majid SA et al (1996) Paracrine regulation of the renal microcirclation. Physiol Rev 76:425–536

    PubMed  CAS  Google Scholar 

  • Nguyen G, Burckle C, Sraer JD (2003) The renin receptor: the facts, the promise and the hope. Curr Opin Nephrol Hypertens 12:51–55

    Article  PubMed  CAS  Google Scholar 

  • Niimura F, Labosky PA, Kakuchi J, Okubo S, Yoshida H, Oikawa T, Ichiki T, Naftilan AJ, Fogo A, Inagami T (1995) Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation. J Clin Invest 96:2947–2954

    Article  PubMed  CAS  Google Scholar 

  • Noda M, Fukuda R, Matsui T et al (1997) Effects of candesartan cilexetil and enalapril in 5/6 nephrectomized rats. Kidney Int 63(Suppl):S136–S139

    CAS  Google Scholar 

  • Nouet S, Nahamias C (2000) Signal transduction from the angiotensin II AT2 receptor. Trends Endocrinol Metab 11:1–6

    Article  PubMed  CAS  Google Scholar 

  • Oliverio MI, Kim HS, Ito M, Le T, Audoly L, Best CF, Hiller S, Kluckman K, Maeda N, Smithies O, Coffman TM (1998) Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptor-mediated blood pressure regulation in mice 1118. Pediatr Nephrol 24:1113–1120

    Google Scholar 

  • Palmer LS, Lee C, Decker RS et al (1997) The effect of angiotensin converting enzyme inhibition and angiotensin II receptor antagonism on obstructed rat bladder. J Urol 158:1100–1104

    Article  PubMed  CAS  Google Scholar 

  • Park JK, Kim SZ, Kim SH et al (1997) Renin angiotensin system in rabbit corpus cavernosm: functional characterization of angiotensin II receptors. J Urol 158:653–658

    Article  PubMed  CAS  Google Scholar 

  • Park JM, Borer JG, Freeman MR et al (1998) Stretch activates heparin-binding EGF-like growth factor expression in bladder smooth muscle cells. Am J Physiol 275:C1247–C1254

    PubMed  CAS  Google Scholar 

  • Park JK, Kim SZ, Kim SH et al (2000) Renin angiotensin system of rabbit clitoral cavernosum: interaction with nitric oxide. J Urol 164:556–561

    Article  PubMed  CAS  Google Scholar 

  • Park JK, Lee SO, Kim YG et al (2002) Role of rho-kinase activity in angiotensin II-induced contraction of rabbit clitoral cavernosum smooth muscle. Int J Impot Res 14:472–477

    Article  PubMed  CAS  Google Scholar 

  • Park JK, Lee SO, Cui WS et al (2005a) Activity of angiotensin peptides in clitoral cavernosum of alloxan induced diabetic rabbit. Eur Urol 48:1042–1050

    Article  PubMed  CAS  Google Scholar 

  • Park K, Shin JW, Oh JK et al (2005b) Restoration of erectile capacity in normotensive aged rats by modulation of angiotensin receptor type 1. J Androl 26:123–128

    PubMed  CAS  Google Scholar 

  • Persson K, Sando JJ, Tuttle JB et al (1995) Protein kinase C in cyclic stretch-induced nerve growth factor production by urinary tract smooth muscle cells. Am J Physiol 269:C1018–C1024

    PubMed  CAS  Google Scholar 

  • Persson K, Pandita RK, Waldeck K, Andersson K-E (1996) Angiotensin II and bladder obstruction in the rat: influence on hypertrophic growth and contractility. Am J Physiol 271:R1186–R1192

    PubMed  CAS  Google Scholar 

  • Peters CA, Carr MC, Lais A et al (1992a) The response of the fetal kidney to obstruction. J Urol 148:503–509

    PubMed  CAS  Google Scholar 

  • Peters CA, Vasavada S, Dator D, Carr M, Shapiro E, Lepor H, McConnell J, Retik AB, Mandell J (1992b) The effect of obstruction on the developing bladder. J Urol 148:491–496

    PubMed  CAS  Google Scholar 

  • Phillips MI, Speakman EA, Kimura B (1993) Levels of angiotensin and molecular biology of the tissue renin angiotensin system. Regul Pept 43:1–20

    Article  PubMed  CAS  Google Scholar 

  • Phull H, Salkini M, Escobar C et al (2007a) The role of angiotensin II in stress urinary incontinence: a rat model. Neurourol Urodyn 26:81–88

    Article  PubMed  CAS  Google Scholar 

  • Phull H, Salkini M, Purves T et al (2007b) Angiotensin II plays a role in acute murine experimental autoimmune cystitis. BJU Int 100:664–667

    Article  PubMed  CAS  Google Scholar 

  • Pimentel JL, Martinez-Maldonado M, Wilcox JN, Wang S, Luo C (1993) Regulation of renin-angiotensin system in unilateral ureteral obstruction. Kidney Int 44:390–400

    Article  PubMed  CAS  Google Scholar 

  • Pimentel JL Jr, Wang S, Martinez-Maldonado M (1994) Regulation of the renal angiotensin II receptor gene in acute unilateral ureteral obstruction. Kidney Int 45:1614–1621

    Article  PubMed  CAS  Google Scholar 

  • Pimentel JL Jr, Montero A, Wang S, Yosipiv I, El-Dahr S, Martinez-Maldonado M (1995a) Sequential changes in renal expression of renin-angiotensin system genes in acute unilateral ureteral obstruction. Kidney Int 48:1247–1253

    Article  PubMed  CAS  Google Scholar 

  • Pimentel JL Jr, Sundell CL, Wang S, Kopp JB, Montero A, Martinez-Maldonado M (1995b) Role of angiotensin II in the expression and regulation of transforming growth factor-beta in obstructive nephropathy. Kidney Int 48:1233–1246

    Article  PubMed  CAS  Google Scholar 

  • Puntmann VO, Hussain MB, Mayr M et al (2005) Role of oxidative stress in angiotensin-II mediated contraction of human conduit arteries in patients with cardiovascular disease. Vascul Pharmacol 43:277–282

    Article  PubMed  CAS  Google Scholar 

  • Purves J, Do R, Heimark R et al (2004) Discovery and population characterization of angiotensin receptors in the proximal urethra of the male mouse. Presented at the Western Section. American Urological Association, San Diego

    Google Scholar 

  • Rees D, Palmer R, Moncada S (1989) Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci 86:3375–3378

    Article  PubMed  CAS  Google Scholar 

  • Robillard JE, Page WV, Mathews MS et al (1995) Differential gene expression and regulation of renal angiotensin II receptor subtypes (AT1 and AT2) during fetal life in sheep. Pediatr Res 38:896–904

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Vita J, Sanchez-Lopez E, Esteban V, Ruperez M, Egido J, Ruiz-Ortega M (2005) Angiotensin II activates the Smad pathway in vascular smooth muscle cells by a transforming growth factor-beta-independent mechanism. Circulation 111:2509–2517

    Article  PubMed  CAS  Google Scholar 

  • Rossi M, Peres LC (1992) Effect of captopril on the prevention and regression of myocardial cell hypertrophy and interstitial fibrosis in pressure overload cardiac hypertrophy. Am Heart J 124:700–709

    Article  PubMed  CAS  Google Scholar 

  • Rubin B, Antonaccio MJ, Goldberg ME et al (1978) Chronic antihypertensives effects of captopril and orally active angiotensin I-converting enzyme inhibitor, in conscious 2-kidney renal hypertensive rats. Eur J Pharmacol 51:592–594

    Article  Google Scholar 

  • Sadjadi J, Kramer GL, Yu CH, Welborn MB 3rd, Modrall JG (2005) Angiotensin II exerts positive feedback on the intrarenal renin-angiotensin system by an angiotensin converting enzyme-dependent mechanism. J Surg Res 129:272–277

    Article  PubMed  CAS  Google Scholar 

  • Sadoshima J, Izumo S (1993) Molecular characterization of angiotensin 11-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype. Circ Res 73:413–423

    PubMed  CAS  Google Scholar 

  • Sadoshima J, Xu Y, Slayter HS, Izumo S (1993) Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 75:977–984

    Article  PubMed  CAS  Google Scholar 

  • Sangaleti CT, Crescenzi A, Michelini LC (2004) Endogenous angiotensin and pressure modulate brain angiotensinogen and AT1A mRNA expression. Hypertension 43:317–323

    Article  PubMed  CAS  Google Scholar 

  • Santis WF, Sullivan MP, Gobet R et al (2000) Characterization of ureteral dysfunction in an experimental model of congenital bladder outlet obstruction. J Urol 163:980–984

    Article  PubMed  CAS  Google Scholar 

  • Santis WF, Peters CA, Yalla AV, Sullivan MP (2003) Ureteral function is modulated by a local renin-angiotensin system. J Urol 170:259–263

    Article  PubMed  CAS  Google Scholar 

  • Shanmugam S, Lorens-Cortes C, Clauser E, Corvol P, Gasc JM (1995) Expression of angiotensin II AT2 receptor mRNA during development of rat kidney and adrenal gland. Am J Physiol Renal Physiol 268:F922–F930

    CAS  Google Scholar 

  • Shapiro E, Becich MJ, Perlman E, Lepor H (1991) Bladder wall abnormalities in myelodysplastic bladders: a computer assisted morphometric analysis. J Urol 145:1024–1029

    PubMed  CAS  Google Scholar 

  • Shirazi M, Noorafshan A, Bahri MA, Hassanpoor A (2008) Captopril reduces deposition of collagen in lamina propria and muscular layers of the bladder and ureter in neonatal dogs with partial urethral obstruction. Scand J Urol Nephrol 42:324–329

    Article  PubMed  CAS  Google Scholar 

  • Sim MK, Chen WS (2006) Effects of losartan on angiotensin receptors in the hypertrophic rat heart. Regul Pept 137:140–146

    Article  PubMed  CAS  Google Scholar 

  • Simon G, Altman S (1992) Subpressor angiotensin I1 is a bifunctional growth factor of vascular muscle in rat. J Hypertens 10:1165–1171

    Article  PubMed  CAS  Google Scholar 

  • Simon G, Abraham G, Altman S (1994) Stimulation of vascular glycosaminoglycan synthesis by subpressor angiotensin II in rats. Hypertension 23:1148–1151

    Google Scholar 

  • Singh R, Mackraj I, Naidoo R, Gathiram P (2006) Sanguinarine downregulates AT1a gene expression in a hypertensive rat model. J Cardiovasc Pharmacol 48:14–21

    Article  PubMed  CAS  Google Scholar 

  • Siragy HM, de Gasparo M, Carey RM (2006) Angiotensin II type 2 receptor-bradykinin B2 receptor functional heterodimerization. Hypertension 48:316–322

    Article  PubMed  CAS  Google Scholar 

  • Steidle CP, Cohen ML, Neubauer BL (1990) Bradykinin-induced contractions of canine prostate and bladder: effect of angiotensin-converting enzyme inhibition. J Urol 144:390–392

    PubMed  CAS  Google Scholar 

  • Takahashi N, Lopez ML, Cowhig JE Jr, Taylor MA, Hatada T, Riggs E, Lee G, Gomez RA, Kim HS, Smithies O (2005) Ren1c homozygous null mice are hypotensive and polyuric, but heterozygotes are indistinguishable from wild-type. J Am Soc Nephrol 16:125–132

    Article  PubMed  Google Scholar 

  • Talaia C, Queiroz G, Pinheiro H, Moura D, Gonçalves J (2006) Involvement of G-protein [beta] [gamma] subunits on the influence of inhibitory [alpha]2-autoreceptors on the angiotensin AT1- receptor modulation of noradrenaline release in the rat vas deferens. Neurochem Int 49:698–707

    Article  PubMed  CAS  Google Scholar 

  • Tanabe N, Ueno A, Tsujimoto G (1993) Angiotensin II receptors in the rat urinary bladder smooth muscle: type 1 subtype receptors mediate contractile responses. J Urol 150:1056–1059

    PubMed  CAS  Google Scholar 

  • Thai H, Wollmuth J, Goldman S, Gaballa M (2003) Angiotensin subtype 1 receptor (AT1) blockade imporves vasorelaxation in heart failure by up-regulation of endothelial nitric-oxide synthase via activation of the AT2 receptor. J Pharmacol Exp Ther 307:1171–1178

    Article  PubMed  CAS  Google Scholar 

  • Anonymous (1991) Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD investigators. N Engl J Med 325:293–302

    Article  Google Scholar 

  • Tipnis SR, Hooper NM, Hyde R et al (2000) A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 275:33238–33243

    Article  PubMed  CAS  Google Scholar 

  • Toblli JE, Stella I, Inserra F, Ferder L, Zeller F, Mazza ON (2000) Morphological changes in cavernous tissue in spontaneously hypertensive rats. Am J Hypertens 13:686–692

    Article  PubMed  CAS  Google Scholar 

  • Toblli JE, Stella I, Mazza ON, Ferder L, Inserra F (2004a) Candesartan cilexetil protects cavernous tissue in spontaneously hypertensive rats. Int J Impot Res 16:305–312

    Article  PubMed  CAS  Google Scholar 

  • Toblli JE, Stella I, Mazza ON, Ferder L, Inserra F (2004b) Different effect of losartan and amlodipine on penile structures in male spontaneously hypertensive rats. Am J Nephrol 24:614–623

    Article  PubMed  CAS  Google Scholar 

  • Toblli JE, Cao G, Lombrana A, Rivero M (2007) Functional and morphological improvement in erectile tissue of hypertensive rats by long-term combined therapy with phosphodiesterase type 5 inhibitor and losartan. J Sex Med 4:1291–1303

    Article  PubMed  CAS  Google Scholar 

  • Touyz RM, Berry C (2002) Recent advances in angiotensin II signaling. Braz J Med Biol Res 35:1001–1015

    Article  PubMed  CAS  Google Scholar 

  • Touyz RM, Schiffrin EL (2001) Increased generation of superoxide by angiotensin II in smooth muscle cells from resistance arteries of hypotensive patients: role of phospholipase D-dependent NADPH oxidase-sensitive pathways. J Hypertens 19:1245–1254

    Article  PubMed  CAS  Google Scholar 

  • Trigo-Rocha F, Hsu GL, Donatucci CF et al (1993) The role of cyclic adenosine monophosphate, cyclic guanosine monophosphate, endothelium and nonadrenergic, noncholinergic neurotransmission in canine penile erection. J Urol 149:872–877

    PubMed  CAS  Google Scholar 

  • Tsuchida S, Matsusaka T, Chen X, Okubo S, Niimura F, Nishimura H, Fogo A, Utsunomiya H, Inagami T, Ichikawa I (1998) Murine double nullizygotes of the angiotensin type 1A and 1B receptor genes duplicate severe abnormal phenotypes of angiotensinogen nullizygotes. J Clin Invest 101:755–760

    Article  PubMed  CAS  Google Scholar 

  • Tsutsumi Y, Matsubara H, Masaki H et al (1999) Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation. J Clin Invest 104:925–935

    Article  PubMed  CAS  Google Scholar 

  • Tulloch AG (1974) The vascular contribution to intraurethral pressure. BJU Int 46:659–664

    Article  CAS  Google Scholar 

  • Uvelius B, Lindner P, Mattiasson A (1991) Collagen content of the rat urinary bladder following removal of an experimental infravesical outlet obstruction. Urol Int 47:245–249

    Article  PubMed  CAS  Google Scholar 

  • Waldeck K, Lindberg BF, Persson K et al (1997) Characterization of angiotensin II formation in human isolated bladder by selective inhibitors of ACE and human chymase: a functional and biochemical study. Br J Pharmacol 121:1081–1086

    Article  PubMed  CAS  Google Scholar 

  • Wang HD, Johns DG, Xu S et al (2002) Role of superoxide anion in regulating pressor and vascular hypertrophic responses to Ang-II. Am J Physiol Heart Circ Physiol 282:H1697–H1702

    PubMed  CAS  Google Scholar 

  • Weber KT, Brilla CG (1991) Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensinaldosteronesystem. Circulation 83:1849–1865

    PubMed  CAS  Google Scholar 

  • White CR, Brock TA, Chang LY (1994) Superoxide and peroxynitrite in atherosclerosis. Proc Natl Acad Sci U S A 91:1044–1048

    Article  PubMed  CAS  Google Scholar 

  • Wong MK, Ge W, Woo NY (2007) Positive feedback of hepatic angiotensinogen expression in silver sea bream (Sparus sarba). Mol Cell Endocrinol 263:103–111

    Article  PubMed  CAS  Google Scholar 

  • Yamada T, Horiuchi M, Dzau VJ (1996) Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci U S A 93:156–160

    Article  PubMed  CAS  Google Scholar 

  • Yamada S, Takeuchi C, Oyunsul L, Ito Y (2009) Bladder angiotensin-II receptors: characterization and alteration I bladder outlet obstruction. Eur Urol 55:482–490

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi O (2004) Response of bladder smooth muscle cells to obstruction: signal transduction and the role of mechanosensors. Urology 63(Suppl 3A):11–16

    Article  PubMed  Google Scholar 

  • Yan C, Kim D, Aizawa T et al (2003) Functional interplay between angiotensin II and nitric oxide. Arterioscler Thromb Vasc Biol 23:26–36

    Article  PubMed  CAS  Google Scholar 

  • Yang R, Yang B, Wen Y et al (2009) Losartan, an angiotensin type I receptor, restores erectile function by downregulation of cavernous renin-angiotensin system in streptozocin-induced diabetic rats. J Sex Med 6:696–707

    Article  PubMed  CAS  Google Scholar 

  • Yayam K, Hiyoshi H, Imazu D, Okamoto H (2006) Angiotensin II stimulates endothelial NO synthase phosphorylation in thoracic aorta of mice with abdominal aortic banding via type 2 receptor. Hypertension 48:958–964

    Article  CAS  Google Scholar 

  • Ye G, Jin X (1997) Action of autonomic drugs on the in vivo bladder base and proximal urethra in dog. Chin Med J (Engl) 110:173–176

    CAS  Google Scholar 

  • Yoo KH, Norwood VF, El-Dahr SS et al (1997) Regulation of angiotensin II, AT1 and AT2 receptors in neonatal ureteral obstruction. Am J Physiol 273:R503–R509

    PubMed  CAS  Google Scholar 

  • Yospiv IV (2009) Renin-angiotensin system-growth factor cross-talk: a novel mechanism for ureteric bud morphogenesis. Pediatr Nephrol 24:1113–1120

    Article  Google Scholar 

  • Yosypiv IV (2004) Hypothesis: a novel role for the renin angiotensin system in ureteric bud branching. Organogenesis 1:26–32

    Article  PubMed  CAS  Google Scholar 

  • Yuan X, Wu S, Lin T et al (2011) Role of nitric oxide synthase in bladder pathologic remodeling and dysfunction resulting from partial outlet obstruction. Urology 77:1008.e1–1008.e8

    Article  Google Scholar 

  • Zhu YC, Zhu YZ, Lu N et al (2003) Role of angiotensin AT1 and AT2 receptor in cardiac hypertrophy and cardiac remodeling. Clin Exp Pharmacol Physiol 30:911–918

    Article  PubMed  CAS  Google Scholar 

  • Zimpelmann J, Burns KD (2001) Angiotensin II AT2 receptors inhibit growth responses in proximal tubule cells. Am J Physiol Renal Physiol 281:F300–F308

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Craig Comiter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Comiter, C. Local renin–angiotensin systems in the genitourinary tract. Naunyn-Schmiedeberg's Arch Pharmacol 385, 13–26 (2012). https://doi.org/10.1007/s00210-011-0706-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-011-0706-y

Keywords

Navigation