Relative contribution of vasodilator prostanoids, NO, and KATP channels to human forearm metabolic vasodilation.
Isolated ATP-sensitive K(+) (K(ATP)) channel inhibition with glibenclamide does not alter exercise-induced forearm metabolic vasodilation. Whether forearm metabolic vasodilation would be influenced by K(ATP) channel inhibition in the setting of impaired nitric oxide (NO)- and prostanoid-mediated vasodilation is unknown. Thirty-seven healthy subjects were recruited. Forearm blood flow (FBF) was assessed using venous occlusion plethysmography, and functional hyperemic blood flow (FHBF) was induced by isotonic wrist exercise. Infusion of N(G)-monomethyl-l-arginine (l-NMMA), aspirin, or the combination reduced resting FBF compared with vehicle (P < 0.05). Addition of glibenclamide to l-NMMA, aspirin, or the combination did not further reduce resting FBF. l-NMMA decreased peak FHBF by 26%, and volume was restored after 5 min (P < 0.05). Aspirin reduced peak FHBF by 13%, and volume repaid after 5 min (P < 0.05). Coinfusion of l-NMMA and aspirin reduced peak FHBF by 21% (P < 0.01), and volume was restored after 5 min (P < 0.05). Addition of glibenclamide to l-NMMA and aspirin did not further decrease FHBF. Vascular K(ATP) channel blockade with glibenclamide does not affect resting FBF or FHBF in the setting of NO and vasodilator prostanoid inhibition.
Farouque
H M Omar
HM
Cardiovascular Research Centre, Monash Medical Centre and Monash University, Melbourne 3168, Victoria, Australia.
Meredith
Ian T
IT
D018528:ATP-Binding Cassette Transporters; D000328:Adult; D001241:Aspirin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015444:Exercise / Q000502:physiology; D005260:Female; D005542:Forearm / Q000098:blood supply* / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D054086:KATP Channels; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D010991:Plethysmography; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011453:Prostaglandins / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D054086:KATP Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011453:Prostaglandins; C092520:uK-ATP-1 potassium channel; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D001241:Aspirin; D005905:Glyburide