Endothelium-dependent relaxation in response to acetylcholine in pregnant guinea-pig uterine artery.
Recently, strong evidence has suggested that nitric oxide (NO) synthesis is significantly increased in the uterine artery during pregnancy, which may mediate the increased blood flow to the uterus that is characteristic of pregnancy. We therefore investigated the nature of the mediators of acetylcholine (ACh)-induced relaxation in pregnant guinea-pig uterine arterial rings. ACh (0.1 nM to 60 microM) induced endothelium-dependent relaxation of phenylephrine-precontracted pregnant guinea-pig uterine artery. N(G)-monomethyl-L-arginine (3-30 microM) antagonized the effect of ACh, with suppression of maximal ACh-induced relaxation, in a concentration-dependent manner. The inhibition of relaxation by N(G)-monomethyl-L-arginine (10 microM) was significantly overcome by L-arginine (10 microM), but not by D-arginine (100 microM). On the contrary, the administration of indomethacin (10 microM) and diethylcarbamazine (100 microM) did not modify the relaxation of guinea-pig uterine artery induced by ACh. The ACh-evoked relaxation was unaltered when K+-rich Krebs-Ringer bicarbonate solution was used to induce tone instead of phenylephrine, or when a nonselective blocker of K+ channels, 4-aminopyridine (6 mM), was applied to phenylephrine-precontracted segments. It is concluded that the relaxation induced by ACh in pregnant guinea-pig uterine artery can be explained entirely by the release of NO from vascular endothelial cells, without involvement of other endothelium-derived relaxing factors, similar to that previously reported for non-pregnant guinea-pig uterine artery. Thus, it seems that increased activity of NO synthase during pregnancy is without significant influence on the ACh action on uterine artery.
Jovanović
A
A
Department of Clinical Pharmacology, Pharmacology and Toxicology, School of Medicine, Belgrade, Yugoslavia.
Jovanović
S
S
Grbović
L
L
D000109:Acetylcholine / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001158:Arteries / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D014599:Uterus / Q000098:blood supply*; D014664:Vasodilation / Q000502:physiology*
D009569:Nitric Oxide; D000109:Acetylcholine