title: Bradykinin dilates rat middle cerebral artery and its large branches via endothelial B2 receptors and release of nitric oxide.
abstract: Ring segments of rat middle cerebral artery (MCA) were prepared for measurement of isometric force and precontracted with 10(-4) M uridine triphosphate (UTP). Concentration-effect curves (CEC) were constructed for bradykinin (BK, 10(-8)(-10)(-1) M) in segments with functionally intact (E+) or denuded (E-) endothelium. E- segments did not dilate to BK. The BK receptor was characterized by application of specific B1 or B2 antagonists [des-Arg4-Leu8] BK (10(-5) M) and [D-Arg4-Hyp3-Thi5-D-Tic7-Oic8] BK (HOE140, 3 x 10(-7) M), respectively, or B2 agonist [des-Arg9] BK (10(-8)-10(-4) M). Involvement of nitric oxide (NO) was tested with NG-nitro-L-arginine (LNNA, 10(-4) M). BK induced concentration-dependent relaxation with a maximal effect (Emax) of 40.86 +/- 1.50% at 10(-4) M and a pD2 (-log10 EC50) of 6.818 +/- 0.044. This relaxation could be prevented with HOE140 or LNNA, but was not influenced by [des-Arg(9)-Leu] BK. [des-Arg9] BK did not induce any effect. These results demonstrate that BK induced relaxation via endothelial B2 receptors and release of NO in isolated rat MCA.
authors.affiliation: Department of Physiology, LMU Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Görlach
authors.forename: M
authors.initials: M
authors.lastname: Wahl
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology; D065168:Bradykinin Receptor Antagonists; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D065168:Bradykinin Receptor Antagonists; D004791:Enzyme Inhibitors; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D019335:Nitroarginine; D009569:Nitric Oxide; C065679:icatibant; D019001:Nitric Oxide Synthase; D001920:Bradykinin