Effect of the vascular endothelium on contractions induced by prostaglandin F2 alpha in isolated pregnant guinea pig uterine artery.
The purpose of this study was to examine the influence of endothelium on prostaglandin F2 alpha-mediated contractions in pregnant guinea pig uterine artery. Consequently, the effects of prostaglandin F2 alpha on pregnant guinea pig uterine arterial rings with both intact and denuded endothelium were studied. In vessels with denuded endothelium prostaglandin F2 alpha (0.1-10 microM) induced contraction (pD2 = 6.17) with greater potency than in vessels with intact endothelium (pD2 = 5.68). NG-Monomethyl-L-arginine (10 microM) did not affect the concentration-response curve for prostaglandin F2 alpha, regardless of endothelial condition. In contrast, in both types of preparation, indomethacin (10 microM) increased the maximal response value obtained with prostaglandin F2 alpha, but this effect was significantly greater in preparations with intact than in those with denuded endothelium (128.3 versus 206.5%). Moreover, indomethacin shifted the concentration-response curve for prostaglandin F2 alpha to the left only in preparations with intact endothelium. The pKA values for prostaglandin F2 alpha itself did not differ between preparations: 5.41 and 5.52 for pregnant guinea pig uterine artery with and without endothelium, respectively. The receptor reserve expressed as KA/EC50 was significantly greater in rings with denuded (4.44) compared to those in rings with intact endothelium (1.86). We conclude that prostaglandin-F2 alpha-induced contraction in pregnant guinea pig uterine artery is modulated by the vascular endothelium. It is probable that cyclooxygenase products relating to vasodilatation and derived from endothelium mediate this effect, acting as a functional endogenous antagonist and thereby reducing the apparent efficacy and potency of prostaglandin F2 alpha.
Grbović
L
L
Department of Pharmacology, Medical Faculty, Belgrade, Yugoslavia.
Jovanović
A
A
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009994:Osmolar Concentration; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D014599:Uterus / Q000098:blood supply*; D014661:Vasoconstriction / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D015237:Dinoprost; D007213:Indomethacin