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 B1 receptor agonist des-Arg9-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-Arg9-bradykinin and lipopolysaccharide, whereas de-endothelized rings responded to lipopolysaccharide but not to des-Arg9-bradykinin. In endothelized preparations, the responses to des-Arg9-bradykinin were inhibited by Nomega-nitro-L-arginine and iberiotoxin. De-endothelized ring responses to lipopolysaccharide were inhibited by iberiotoxin, glibenclamide and B1 antagonist Lys-[Leu8,des-Arg9]-bradykinin. This antagonist also inhibited hyperpolarization by des-Arg9-bradykinin and by the á2-adrenoceptor agonist, brimonidine. Our results indicate that Ca(2+)-sensitive K+ channels are the final mediators of the responses to des-Arg9-bradykinin, whereas both Ca(2+)- and ATP-sensitive K+ channels mediate the responses to lipopolysaccharide. The inhibitory effects of Lys-[Leu8,des-Arg9]-bradykinin is due to a direct action on Ca(2+)- and ATP-sensitive potassium channels.
Farias
Nelson C
NC
Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu, 862, 04023-062 São Paulo, SP, Brazil.
Feres
Teresa
T
Paiva
Antonio C M
AC
Paiva
Therezinha B
TB
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D019806:Cromakalim / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D007609:Kallidin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors* / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
D008070:Lipopolysaccharides; D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D011810:Quinoxalines; D014665:Vasodilator Agents; C082229:bradykinin, Lys-Leu(8)-desArg(9)-; D019806:Cromakalim; C024626:bradykinin, des-Arg(9)-; D007609:Kallidin; D000068438:Brimonidine Tartrate; C064719:iberiotoxin; D000255:Adenosine Triphosphate; D000109:Acetylcholine; D001920:Bradykinin