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.
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Abadir PM, Periasamy A, Carey RM, Siragy HM (2006) Angiotensin II type 2 receptor-bradykinin B2 receptor functional heterodimerization. Hypertension 48:316–322
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
Andersson K-E (2003) Erectile physiological and pathophysiological pathways involved in erectile dysfunction. J Urol 170:S6–S14
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
Ardaillo R, Chansel D (1997) Synthesis and effects of active fragments of angiotensin II. Kidney Int 52:1458–1468
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
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
Bader M, Ganten D (2008) Update on tissue renin–angiotensin systems. J Mol Med 86:615–621
Batenburg WW, Garrelds IM, Bernasonic CC et al (2004) Angiotensin II type 2 receptor-mediated vasodilation in human coronary microareteries. Circulation 109:2296–2301
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
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
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
Border WA, Noble NA (1998) Interactions of transforming growth factor-beta and angiotensin II in renal fibrosis. Hypertension 31:181–188
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
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
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
Burnett AL (1997) Nitric oxide in the penis: physiology and pathology. J Urol 157:320–324
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
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
Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular disease: the role of oxidative stress. Circ Res 87:840–844
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
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
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
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
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
Chicurel ME, Chen CS, Ingber DE (1998) Cellular control lies in the balance of forces. Curr Opin Cell Biol 10:232–239
Cohn JN (2006) What is the role of angiotensin-receptor blockade in cardiovascular protection? Am Heart J 152(859):e.1–e.8
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
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
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
Darby IA, Congiu M, Fernley RT (1994) Cellular and ultrastructural location of antiotensinogen in rat and sheep kidney. Kidney Int 46:1557–1560
de Gasparo M (2002) Angiotensin II and nitric oxide interaction. Heart Fail Rev 7:347–358
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
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
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
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
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
Dzielak DJ (1992) The immune system and hypertension. Hypertension 19(Suppl):I36–I44
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
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
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
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
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
Freeman EJ, Tallant EA (1994) Vasclar smooth-muscle cells contain AT1 angiotensin receptors coupled to phospholipase D activation. Biochem J 304:543–548
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
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
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
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
Goldstein I, Berman JR (1998) Vasculogenic female sexal dysfnction: vaginal engorgement and clitoral erectile insufficiency syndromes. Int J Impot Res 10:S84–S90
Greenland JE, Brading AF (1997) The in vivo and in vitro effects of hypoxia on pig urethral smooth muscle. BJU Int 79:525–531
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
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
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
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
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
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
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
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
Jin L-M (2009) Angiotensin II signaling and its implication in erectile dysfunction. J Sex Med 6(suppl 3):302–210
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
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
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
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
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
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
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
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
Kim KM, Kogan BA, Massad CA, Huang YC (1991) Collagen and elastin in the obstructed fetal bladder. J Urol 146:528–531
Klahr S, Morrissey JJ (1997) Comparative study of ACE inhibitors and angiotensin II receptor antagonists in interstitial scarring. Kidney Int 52:S111–S114
Klett CP, Printz MP, Bader M, Ganten D, Eggena P (1996) Angiotensinogen messenger RNA stabilization by angiotensin II. J Hypertens Suppl 14:S25–S36
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
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
Leiblum SR, Bame RM, Croog SH (1994) The sexual functioning of elderly hypertensive women. J Sex Marital Ther 20:250–270
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
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
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
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
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
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
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
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
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
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
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
Morrissey JJ, Klahr S (1997) Enalapril decreases nuclear factor kappa B activation in the kidney with ureteral obstruction. Kidney Int 52:926–933
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
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
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
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
Navar LG, Inscho EW, Majid SA et al (1996) Paracrine regulation of the renal microcirclation. Physiol Rev 76:425–536
Nguyen G, Burckle C, Sraer JD (2003) The renin receptor: the facts, the promise and the hope. Curr Opin Nephrol Hypertens 12:51–55
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
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
Nouet S, Nahamias C (2000) Signal transduction from the angiotensin II AT2 receptor. Trends Endocrinol Metab 11:1–6
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
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
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
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
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
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
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
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
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
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
Peters CA, Carr MC, Lais A et al (1992a) The response of the fetal kidney to obstruction. J Urol 148:503–509
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
Phillips MI, Speakman EA, Kimura B (1993) Levels of angiotensin and molecular biology of the tissue renin angiotensin system. Regul Pept 43:1–20
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Sangaleti CT, Crescenzi A, Michelini LC (2004) Endogenous angiotensin and pressure modulate brain angiotensinogen and AT1A mRNA expression. Hypertension 43:317–323
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
Santis WF, Peters CA, Yalla AV, Sullivan MP (2003) Ureteral function is modulated by a local renin-angiotensin system. J Urol 170:259–263
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
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
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
Sim MK, Chen WS (2006) Effects of losartan on angiotensin receptors in the hypertrophic rat heart. Regul Pept 137:140–146
Simon G, Altman S (1992) Subpressor angiotensin I1 is a bifunctional growth factor of vascular muscle in rat. J Hypertens 10:1165–1171
Simon G, Abraham G, Altman S (1994) Stimulation of vascular glycosaminoglycan synthesis by subpressor angiotensin II in rats. Hypertension 23:1148–1151
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
Siragy HM, de Gasparo M, Carey RM (2006) Angiotensin II type 2 receptor-bradykinin B2 receptor functional heterodimerization. Hypertension 48:316–322
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
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
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
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
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
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
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
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
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
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
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
Touyz RM, Berry C (2002) Recent advances in angiotensin II signaling. Braz J Med Biol Res 35:1001–1015
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
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
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
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
Tulloch AG (1974) The vascular contribution to intraurethral pressure. BJU Int 46:659–664
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
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
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
Weber KT, Brilla CG (1991) Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensinaldosteronesystem. Circulation 83:1849–1865
White CR, Brock TA, Chang LY (1994) Superoxide and peroxynitrite in atherosclerosis. Proc Natl Acad Sci U S A 91:1044–1048
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
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
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
Yamaguchi O (2004) Response of bladder smooth muscle cells to obstruction: signal transduction and the role of mechanosensors. Urology 63(Suppl 3A):11–16
Yan C, Kim D, Aizawa T et al (2003) Functional interplay between angiotensin II and nitric oxide. Arterioscler Thromb Vasc Biol 23:26–36
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
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
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
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
Yospiv IV (2009) Renin-angiotensin system-growth factor cross-talk: a novel mechanism for ureteric bud morphogenesis. Pediatr Nephrol 24:1113–1120
Yosypiv IV (2004) Hypothesis: a novel role for the renin angiotensin system in ureteric bud branching. Organogenesis 1:26–32
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
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
Zimpelmann J, Burns KD (2001) Angiotensin II AT2 receptors inhibit growth responses in proximal tubule cells. Am J Physiol Renal Physiol 281:F300–F308
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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
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DOI: https://doi.org/10.1007/s00210-011-0706-y