Lys-[Leu8,des-Arg9]-bradykinin blocks lipopolysaccharide-induced SHR aorta hyperpolarization by inhibition of Ca++- and ATP-dependent K+ channels

The mediators involved in the hyperpolarizing effects of lipopolysaccharide and of the bradykinin B, receptor agonist des-Arg(9)-bradykinin on the rat aorta were investigated by comparing the responses of aortic rings of spontaneously hypertensive and normotensive Wistar rats. Endothelized rings from hypertensive rats were hyperpolarized by des-Arg(9)-bradykinin and lipopolysaccharide, whereas deendothelized rings responded to lipopolysaccharide but not to des-Arg(9)-bradykinin. In endothelized preparations, the responses to des-Arg(9)-bradykinin were inhibited by N-nitro-L-arginine and iberiotoxin. De-endothelized ring responses to lipopolysaccharide were inhibited by iberiotoxin, glibenclamide and B, antagonist Lys-[Leu(8),des-Arg(9)]-bradykinin. This antagonist also inhibited hyperpolarization by des-Arg(9)-bradykinin and by the a(2)-adrenoceptor agonist, brimonidine. Our results indicate that Ca2+-sensitive K+ channels are the final mediators of the responses to des-Arg(9)-bradykinin, whereas both Ca2+- and ATP-sensitive K+ channels mediate the responses to lipopolysaccharide. The inhibitory effects of Lys-[Leu(8),des-Arg(9)]-bradykinin is due to a direct action on Ca2+- and ATP-sensitive potassium channels. (C) 2004 Elsevier B.V All rights reserved.