Lys-[Leu 8,des-Arg 9]-bradykinin blocks lipopolysaccharide-induced SHR aorta hyperpolarization by inhibition of Ca ++- and ATP-dependent K + channels

• Published in: European journal of pharmacology 2004-09, Vol.498 (1), p.163-169
• Main Authors: Farias, Nelson C., Feres, Teresa, Paiva, Antonio C.M., Paiva, Therezinha B.
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Adenosine Triphosphate - physiology; Animals; Aorta; Aorta, Thoracic - drug effects; Aorta, Thoracic - physiology; Biological and medical sciences; Bradykinin - analogs & derivatives; Bradykinin - pharmacology; Brimonidine Tartrate; Cromakalim - pharmacology; Des-Arg 9-bradykinin; Dose-Response Relationship, Drug; Endothelium, Vascular - physiology; In Vitro Techniques; K + channel; Kallidin - analogs & derivatives; Kallidin - pharmacology; Lipopolysaccharide; Lipopolysaccharides - pharmacology; Male; Medical sciences; Membrane Potentials - drug effects; Peptides - pharmacology; Pharmacology. Drug treatments; Potassium Channels, Calcium-Activated - antagonists & inhibitors; Potassium Channels, Calcium-Activated - physiology; Quinoxalines - pharmacology; Rat, spontaneously hypertensive; Rats; Rats, Inbred SHR; Rats, Wistar; Vasodilator Agents - pharmacology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2004.07.002

The mediators involved in the hyperpolarizing effects of lipopolysaccharide and of the bradykinin B 1 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 de-endothelized 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 ω-nitro- l-arginine and iberiotoxin. De-endothelized ring responses to lipopolysaccharide were inhibited by iberiotoxin, glibenclamide and B 1 antagonist Lys-[Leu 8,des-Arg 9]-bradykinin. This antagonist also inhibited hyperpolarization by des-Arg 9-bradykinin and by the á 2-adrenoceptor agonist, brimonidine. Our results indicate that Ca 2+-sensitive K + channels are the final mediators of the responses to des-Arg 9-bradykinin, whereas both Ca 2+- 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 Ca 2+- and ATP-sensitive potassium channels.