title: Signal transduction pathways involved in kinin B(2) receptor-mediated vasodilation in the rat isolated perfused kidney.
abstract: The signal transduction pathways involved in kinin B(2) receptor-related vasodilation were investigated in rat isolated perfused kidneys. During prostaglandin F(2alpha) or KCl-induced constriction, the vasodilator response to a selective B(2) receptor agonist, Tyr(Me)(8)bradykinin (Tyr(Me)(8)BK), was assessed. Tyr(Me)(8)BK produced a concentration- and endothelium-dependent relaxation that was decreased by about 30 - 40% after inhibition of nitric oxide (NO) synthase by N(G)-nitro-L-arginine (L-NOARG) or of cyclo-oxygenase by indomethacin; a greater decrease (about 40 - 50%) was observed after concomitant inhibition of the two pathways. High extracellular K(+) diminished Tyr(Me)(8)BK-induced relaxation by about 75% suggesting a major contribution of endothelium-derived hyperpolarization. The residual response was almost completely suppressed by NO synthase and cyclo-oxygenase inhibition. The K(+) channel inhibitors, tetrabutylammonium (non-specific) and charybdotoxin (specific for Ca(2+)-activated K(+) channel), suppressed Tyr(Me)(8)BK-induced relaxation resistant to L-NOARG and indomethacin. Inhibition of cytochrome P450 (clotrimazole or 7-ethoxyresorufin) decreased the NO/prostanoids-independent relaxation to Tyr(Me)(8)BK by more than 60%, while inhibition of the cannabinoid CB(1) receptor (SR 141716A) had only a moderate effect. Acetylcholine induced a concentration-dependent relaxation with characteristics nearly similar to the response to Tyr(Me)(8)BK. In contrast, the relaxation elicited by sodium nitroprusside was potentiated in the absence of NO (L-NOARG or removal of endothelium) but remained unchanged otherwise. These results indicate that the activation of kinin B(2) receptors in the rat isolated kidney elicits an endothelium-dependent vasorelaxation, mainly dependent on the activation of charybdotoxin-sensitive Ca(2+)-activated K(+) channels. In addition, cytochrome P450 derivatives appear to be involved.
authors: Institut de Pharmacologie, Faculté de Médecine, 11 rue Humann, 67085 Strasbourg Cedex, France.
authors: K
authors: K
authors: Bagaté
authors: M
authors: M
authors: Grima
authors: J L
authors: JL
authors: Imbs
authors: W D
authors: WD
authors: Jong
authors: J J
authors: JJ
authors: Helwig
authors: M
authors: M
authors: Barthelmebs
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000502:physiology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002186:Cannabinoids / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000502:physiology*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D001685:Biological Factors; D065168:Bradykinin Receptor Antagonists; D002186:Cannabinoids; D016861:Cyclooxygenase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C114203:bradykinin, Tyr(Me)8-; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000109:Acetylcholine; D011188:Potassium; D001920:Bradykinin