Responses of the human submandibular artery to ACh and VIP.
Endothelial vasodilatory substances may play a central role in the local regulation of vascular tone. We hypothesized that these substances can mediate endothelium-dependent vasodilatory responses to acetylcholine (ACh) and vasoactive intestinal peptide (VIP) in the human submandibular artery. We evaluated the contributions of endothelial vasodilatory substances to vessel relaxation in response to ACh and VIP, using different inhibitors of endothelial vasodilation, the nitric oxide synthase inhibitor, the cyclo-oxygenase inhibitor, indomethacin, the potassium channel blocker, and 4-aminopyridine. ACh and VIP caused an endothelium- and concentration-dependent relaxation in this artery. ACh relaxation was completely blocked after the concomitant addition of N(G)-nitro-L-arginine and indomethacin. The vasorelaxant effect of ACh was not influenced by 4-aminopyridine. VIP relaxation was almost completely abolished by 4-aminopyridine, and was partly inhibited by N(G)-nitro-L-arginine, but was not affected by indomethacin. Thus, in the human submandibular artery, ACh and VIP produced endothelium-dependent vasodilation with different underlying mechanisms: release of nitric oxide (NO) and cyclo-oxygenase products for ACh, and release of NO and endothelium-derived hyperpolarizing factor for VIP.
Stojić
D
D
Department of Pharmacology, Faculty of Stomatology, University of Belgrade, Dr. Subotića br. 8, 11 000 Belgrade. miona-25@beotel.yu
Pesić
S
S
Radenković
M
M
Popović-Roganović
J
J
Pesić
Z
Z
Grbović
L
L
D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000328:Adult; D001158:Arteries / Q000187:drug effects; D018678:Cholinergic Agents / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D045462:Endothelium-Dependent Relaxing Factors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D013363:Submandibular Gland / Q000098:blood supply*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D018678:Cholinergic Agents; D016861:Cyclooxygenase Inhibitors; D045462:Endothelium-Dependent Relaxing Factors; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D019335:Nitroarginine; D014660:Vasoactive Intestinal Peptide; D015761:4-Aminopyridine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D007213:Indomethacin