The relaxant effect of vasoactive intestinal polypeptide in the isolated canine uterine artery: the role of endothelium.
The purpose of this study was to examine the effect of vasoactive intestinal polypeptide (VIP) on the uterine artery obtained from non-pregnant dogs. VIP (3 x 10(-9)-3 x 10(-7) M) induced concentration-dependent relaxation in canine uterine arteries with intact endothelium, pre-contracted with 10(-5) M phenylephrine (pEC(50) = 7.52 +/- 0.02, maximal response was 82.19 +/- 2.15%, n = 36). The administration of the cyclooxygenase inhibitor indomethacin (10(-5) M) or 4-aminopyridine (4-AP), a blocker of potassium channels (10(-5) M), did not modify the relaxation induced by VIP. Contrary to this, N(G)-nitro-L-arginine (L-NOARG) (10(-5) M) inhibited relaxation is evoked by VIP. Indomethacin applied with L-NOARG did not provoke further inhibition of VIP-induced relaxation. In the presence of both L-NOARG and L-NOARG + indomethacin, 4-AP led to the further inhibition of VIP-induced relaxation of canine uterine artery. It is concluded that VIP induces endothelium-dependent relaxation of uterine arteries of non-pregnant dogs, which can be entirely explained by the production of nitric oxide (NO) from the endothelial cells. We proposed that when NO synthesis is inhibited, VIP induces further relaxation, independent of the edothelium-derived relaxing factors, probably through activation of K(+) channels.
Pesić
S
S
Department of Pharmacology, Medical Faculty, 81 Braće Tasković, 18000 Nis-YU, Serbia and Montenegro. srdjan@medfak.medfak.ni.ac.yu
Grbović
L
L
Radenković
M
M
Stojić
D
D
Nikolić
V
V
Cvetković
Z
Z
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001158:Arteries; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D014599:Uterus / Q000098:blood supply*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D015761:4-Aminopyridine; D007213:Indomethacin