Induction of bradykinin B1 receptor-mediated relaxation in the isolated rabbit carotid artery

doi:10.1016/0014-2999(93)90976-O

European Journal of Pharmacology

Volume 239, Issues 1–3, 3 August 1993, Pages 63-67

https://doi.org/10.1016/0014-2999(93)90976-O Get rights and content

Abstract

Responses to bradykinin and to the bradykinin B₁ receptor agonist des-Arg⁹-bradykinin were studied in freshly isolated rabbit carotid artery rings and in rings after a 5-h period of incubation. In freshly isolated rings precontracted with noradrenaline, neither bradykinin nor des-Arg⁹-bradykinin changed the tension whereas acetylcholine relaxed the vessel in a concentration-dependent manner. After incubation, des-Arg⁹-bradykinin, and to a lesser extent bradykinin, produced an endothelium-dependent relaxation. This response was abolished by endothelium removal, N^ω-nitro-L-arginine or cycloheximide but was unaffected by indomethacin. In contrast, the response to acetylcholine was unaffected by cycloheximide and was partially inhibited by N^ω-nitro-L-arginine. In addition, the relaxation curve for des-Arg⁹-bradykinin was markedly shifted (44-fold) by the selective bradykinin B₁ receptor antagonist, des-Arg⁹-[Leu⁸]bradykinin (3 μM) was was unaffectedly by the bradykinin B₂ receptor antagonist, Hoe 140 (1 μM). We conclude that in vitro incubation of the rabbit carotid artery induced endothelial bradykinin B₁ receptors coupled to the release of endothelium-derived nitric oxide.

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Cited by (43)

Effects of dexamethasone and protein kinase C inhibitors on the induction of bradykinin B<inf>1</inf> mRNA and the bradykinin B<inf>1</inf> receptor-mediated contractile response in isolated rat ileum
2002, Biochemical Pharmacology
Citation Excerpt :
cDNAs for B2 and B1 receptors of humans, rabbits, mice, and rats have been cloned [6–11]. Moreover, in addition to isolated blood vessels, several isolated organs, such as colon, intestine, urinary bladder, and murine trachea were reported to express the B1 receptor after the animals had received bacterial LPS or were exposed to certain stimuli [12–20]. The significance of BK B1 receptor induction in some cardiovascular disorders has been reported recently [21–24].
We detected the expression of inducible bradykinin (BK) B₁ receptor mRNA in the rat ileum by the reverse transcriptase–polymerase chain reaction (RT–PCR) method, when the isolated ileum was suspended for at least 1 hr in an aerated Tyrode’s solution at 37°. The induction of this mRNA was both time- and temperature-dependent, and was followed by a contractile response to des-Arg⁹-BK at around 3 hr of incubation; this response increased in magnitude with time and was maximal at 6 hr. In contrast, the contraction in response to BK and the expression of B₂ receptor mRNA were constant throughout this 6-hr incubation period. The contraction due to des-Arg⁹-BK was selectively suppressed by B₁ receptor antagonists, i.e. des-Arg⁹[Leu⁸]-BK and des-Arg¹⁰-HOE140, but not by the B₂ antagonists d-Arg-[Hyp³,Thi^5,8,d-Phe⁷]-BK and HOE140. The inducible des-Arg⁹-BK contractile response was suppressed by continuous in vitro exposure of the ileum to cycloheximide or actinomycin D, but neither inhibitor affected the contraction induced by BK, suggesting that the B₁ receptor could be induced de novo. In vitro and ex vivo treatment of the ileum with dexamethasone suppressed the induction of the contractile response to des-Arg⁹-BK, but had no significant effect on the expression of B₁ receptor mRNA. Some protein kinase C inhibitors, i.e. H7 and calphostin C, suppressed the expression of B₁ receptor mRNA and diminished the contractile response to des-Arg⁹-BK. These results suggest that the de novo synthesis of the B₁ receptor in the ileum preparation can be up-regulated at the transcriptional level (a process in which a specific isoform of protein kinase C may be involved). Additionally, these data suggest that the contractile response to des-Arg⁹-BK involves a process sensitive to some post-transcriptional action of dexamethasone.
Lipopolysaccharide decreases bradykinin receptor-induced acidification responses in cultured bovine aortic endothelial cells
2000, European Journal of Pharmacology
The effects of bacterial lipopolysaccharide (Escherichia coli 0127-B8) on bradykinin receptor function in bovine aortic endothelial cells were investigated using a microphysiometer. Bradykinin and Lys⁰–desArg¹⁰-bradykinin produced concentration-dependent acidification responses with pEC₅₀ values of 8.87±0.20 and 9.78±0.08, respectively. These responses were competitively and selectively antagonised by the bradykinin B₂ receptor antagonist, icatibant and the bradykinin B₁ receptor antagonist, desArg⁹–Leu⁸-bradykinin, respectively. The non-peptide bradykinin B₂ receptor antagonist, FR173657 (0.3 and 3 nM), selectively antagonised bradykinin-induced acidification responses, causing rightward shifts of the concentration–response curves to bradykinin, but at the same time, significantly decreasing the maximum response. A preincubation with lipopolysaccharide (0.01 and 0.1 μg/ml) for 24 h caused a significant concentration-dependent decrease in maximal response to bradykinin (27.2±1.9 and 9.7±0.4% of control) and the bradykinin B₁ receptor agonist, Lys⁰–desArg¹⁰-bradykinin (59.0±7.14 and 25.3±7.8% of control), without affecting the EC₅₀. These results suggest that bradykinin B₁ receptors are constitutively expressed in cultured bovine aortic endothelial cells and that the microphysiometer provides a rapid, sensitive technique to characterise bradykinin receptors and investigate their regulation by cytokines. Interactions between bradykinin receptors and lipopolysaccharide may play a part in the cascade of deleterious effects that occur during septic shock.
Comparative relaxant effects of the NO donors sodium nitroprusside, DEA/NO and SPER/NO in rabbit carotid arteries
1999, General Pharmacology
- 1.
  Sodium nitroprusside (SNP, 10⁻⁹–3×10⁻⁴ M), diethylamine/NO complex (DEA/NO, 10⁻⁹–10⁻⁴ M) and spermine/NO complex (SPER/NO, 10⁻⁸–3×10⁻⁴ M) induced concentration-dependent relaxation of isolated rabbit carotid arteries precontracted with KCl (50 mM) or with histamine (3×10⁻⁶ M).
- 2.
  In KCl-precontracted arteries the order of potency was SNP=DEA/NO>SPER/NO, and in histamine-precontracted arteries the order of potency was SNP>DEA/NO>SPER/NO. Relaxations to the three NO donors were significantly higher in histamine-precontracted arteries than in KCl-precontracted arteries.
- 3.
  The guanylyl cyclase inhibitor methylene blue (10⁻⁵ M) significantly inhibited relaxations to the three NO donors in histamine-precontracted arteries and, to a lesser extent, in KCl-precontracted arteries.
- 4.
  In conclusion, the NO donors SNP, DEA/NO and SPER/NO induce quantitatively different relaxation of rabbit carotid artery. Both, lower relaxant effects in depolarized arteries and inhibition of relaxation by methylene blue indicate the mediation of cGMP formation in the relaxant effects of the three NO donors.
Potent antihypertrophic effect of the bradykinin B2 receptor system on the renal vasculature
1999, Kidney International
Potent antihypertrophic effect of the bradykinin B2 receptor system on the renal vasculature.
Angiotensin type 1 (AT1) receptor-deficient mice (Agtr1-/-), which selectively lack both AT1A and AT1B receptor genes, are characterized by marked intrarenal vascular thickening. In the present study, we explored the possible involvement of the kinin-kallikrein system in the development of this renal vascular hypertrophy.
Wild-type and Agtr1-/- mice were examined for the developmental regulation pattern of the kinin-kallikrein system and treated with aprotinin (a kallikrein inhibitor), AcLys [D-b Nal⁷, Ile⁸] des-Arg⁹-bradykinin (a bradykinin B1 receptor antagonist), or Hoe-140 (a bradykinin B2 receptor antagonist) from 3 to 14 days of age.
The normal postnatal up-regulation of kininase II was organ-specifically suppressed in Agtr1-/- kidneys at 2 and 3 weeks of age. Immunohistochemical staining in Agtr1-/- mice revealed tissue kallikrein staining along the nephron from connecting tubules to cortical collecting tubules in proximity to the hypertrophic vasculature, whereas tissue kallikrein staining was confined to connecting tubules in wild-type mice. Aprotinin and Hoe-140 accelerated the vascular hypertrophy significantly as determined by wall thickness ratio, whereas B1 receptor antagonism had no effect.
The kinin-kallikrein system in the Agtr1-/- mouse kidney is functionally activated by local suppression of kininase II and extensive redistribution of kallikrein to perivascular areas. This activation, specific to the kidney, serves to dampen a development of the marked vascular hypertrophy. These results demonstrate, to our knowledge for the first time, the antihypertrophic effect of the bradykinin B2 receptor system on the renal vasculature in vivo.
Interleukin 8 (IL-8) induces the expression of kinin B<inf>1</inf> receptor in human lung fibroblasts
1998, Biochemical and Biophysical Research Communications
Kinin B₁receptors are induced by various inflammatory mediators. The aim of the present study was to investigate the effect of the CXC chemokine IL-8 on kinin B₁receptor expression in IMR-90 cells, by performing binding studies and Northern blot analysis of B₁receptor mRNA levels. We demonstrated here that the density of the kinin B₁receptors could be increased by the chemokine IL-8 in a concentration- and time-dependent manner. IL-8 also increased the kinin B₁receptor mRNA level in IMR-90 cells. IL-8-induced B₁receptor expression could be totally abolished by pretreatment with the metabolic inhibitors. Furthermore, expression was markedly reduced by antibodies to human IL-1β. In conclusion, IL-8 increased the expression of kinin B₁receptors in IMR-90 cells and this effect is likely to be secondary to the production of IL-1β.
Kinin B<inf>2</inf> and B<inf>1</inf> receptor-mediated vasoactive effects in rabbit synovium
1998, Peptides
Cambridge H. and S. D. Brain. Kinin B₂ and B₁ receptor-mediated vasoactive effects in rabbit synovium.Peptides 19(3) 569–576, 1998.—Blood flow in response to bradykinin (BK, B₂ receptor agonist) and desArg⁹ BK (B₁ receptor agonist) was measured by laser Doppler flowmetry, as a reversal of noradrenaline (50 nmol)-induced decreased blood flow, in the synovium of the anaesthetised rabbit. Either a pretreatment (-6 h) of the cytokines IL-1β (10 pmol) plus TNFα (10 pmol) or saline was injected intra-articularly. BK increased blood flow irrespective of pretreatment, whereas desArg⁹BK increased blood flow only in the cytokine-pretreated joints. The B₂ antagonist HOE 140 reversed (p < 0.01) only the BK responses, and the B₁ antagonist desArg⁹Leu⁸BK only reversed desArg⁹BK responses (p < 0.001). A nitric oxide synthase inhibitor, (L-NAME, 10 μmol kg⁻¹), reversed the effects of the kinins (p < 0.05), but not sodium nitroprusside-stimulated responses. The results suggest that the B₂ receptor is constitutively expressed and that the B₁ receptor can mediate responses in inflamed tissues. The results, in addition, indicate that the responses, mediated via both receptors, are nitric oxide-dependent.

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Induction of bradykinin B1 receptor-mediated relaxation in the isolated rabbit carotid artery

Abstract

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Release of different relaxing factors by cultured porcine endothelial cells

Circ. Res.

Studies on the induction of pharmacological responses to des-Arg9-bradykinin in vitro and in vivo

Br. J. Pharmacol.

Neutral endopeptidase and angiotensin converting enzyme inhibitors potentiate kinin-induced contraction of ferret trachea

J. Pharmacol. Exp. Ther.

Induction of bradykinin B₁ receptor-mediated relaxation in the isolated rabbit carotid artery

Studies on the induction of pharmacological responses to des-Arg⁹-bradykinin in vitro and in vivo