ENDOTHELIUM-DEPENDENT RELAXATION IN RESPONSE TO ACETYLCHOLINE IN PREGNANT GUINEA-PIG UTERINE ARTERY

Recently, strong evidence has suggested that nitric oxide (NO) synthes is is significantly increased in the uterine artery during pregnancy, which may mediate the increased blood flow to the uterus that is chara cteristic of pregnancy, We therefore investigated the nature of the me diators of acetylcholine (ACh)-induced relaxation in pregnant guineapi g uterine arterial rings, ACh (0.1 nM to 60 mu M) induced endothelium- dependent relaxation of phenylephrine-precontracted pregnant guinea-pi g uterine artery, N-G-monomethyl-L-arginine (3-30 mu M) antagonized th e effect of ACh, with suppression of maximal ACh-induced relaxation, i n a concentration-dependent manner. The inhibition of relaxation by N- G-monomethyl-L-arginine (10 mu M) was significantly overcome by L-argi nine (10 mu M), but not by D-arginine (100 mu M). On the contrary, the administration of indomethacin (10 mu M) and diethylcarbamazine (100 mu M) did not modify the relaxation of guinea-pig uterine artery induc ed by ACh, The ACh-evoked relaxation was unaltered when K+-rich Krebs- Ringer bicarbonate solution was used to induce tone instead of phenyle phrine, or when a nonselective blocker of K+ channels, 4-aminopyridine (6 mM), was applied to phenylephrine-precontracted segments. It is co ncluded that the relaxation induced by ACh in pregnant guinea-pig uter ine artery can be explained entirely by the release of NO from vascula r 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 A Ch action on uterine artery.