Mechanism of bradykinin-induced venodilation in humans.
Bradykinin, a nonapeptide, dilates vascular smooth muscle at least in part via endothelial cell-dependent mechanisms. The aim of this study was to examine the action of bradykinin in human veins in vivo. Utilizing the dorsal hand vein technique, dose-response curves to bradykinin (maximum dose = 513 ng/min) were constructed in veins preconstricted with the alpha-adrenergic agonist phenylephrine in healthy young volunteers. Bradykinin almost fully dilated the veins back to their baseline diameter. To determine if desensitization of bradykinin-mediated vasodilation occurs, two bradykinin dose-response curves were constructed with a short (10 min) interval between studies. The second dose-response curve showed a diminished response. The EMAX of the first curve was 97.8 +/- 47.4% dilation and the EMAX of the second curve was 64.3 +/- 28.0% dilation (p < 0.05). However, when the two curves were separated by 40 min, there was no loss of responsiveness. To investigate the mechanism by which bradykinin caused vasodilation, we used methylene blue to antagonize endothelium-derived relaxing factor, and indomethacin to block prostaglandin-dependent effects. Methylene blue partially antagonized the vasodilatory response to bradykinin, decreasing the EMAX by 50%. Indomethacin also partially antagonized the vasodilatory response, but to a lesser extent than did methylene blue. The vasodilatory response to bradykinin was not fully antagonized with concurrent infusion of both methylene blue and indomethacin. The mechanism of bradykinin-induced vasodilation involves both EDRF and prostacyclin, and possibly another, as yet unidentified, mediator as well.(ABSTRACT TRUNCATED AT 250 WORDS)
Dachman
W D
WD
Division of Clinical Pharmacology, Stanford University Medical Center, California.
Ford
G A
GA
Blaschke
T F
TF
Hoffman
B B
BB
D000328:Adult; D000527:Alprostadil / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D006225:Hand / Q000098:blood supply; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue; D009569:Nitric Oxide / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D010656:Phenylephrine; D009569:Nitric Oxide; D011464:Epoprostenol; D000527:Alprostadil; D001920:Bradykinin; D008751:Methylene Blue; D007213:Indomethacin