Bradykinin dilates rat middle cerebral artery and its large branches via endothelial B-2 receptors and release of nitric oxide

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(-5) 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 B-1 or B-2 antagonists [des-Arg(9)-Leu(8)]BK (10(-5) M) and [D-Arg(0)-Hyp(3)-Thi(5)-D-Tic(7)-Oic(8)]BK (HOE140, 3 x 10(-7) M), respectively, or B-1 agonist [des-Arg(9)]BK (10(-8)-10(-4) M). Involvement of nitric oxide (NO) was tested with N-G-nitro-L-arginine (LNNA, 10(-4) M). BK induced concentration-dependent relaxation with a maximal effect (E(max)) of 40.86 +/- 1.50% at 10(-6) M and a pD(2) (-log(10) EC(50)) of 6.818 +/- 0.044. This relaxation could be prevented with HOE140 or LNNA, but was not influenced by [des-Arg(9)-Leu(8)]BK. [des-Arg(9)]BK did not induce any effect. These results demonstrate that BK induced relaxation via endothelial B-2 receptors and release of NO in isolated rat MCA. Copyright (C) 1996 Elsevier Science Inc.