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.