Comparative relaxant effects of YC-1 and DETA/NO on spontaneous contractions and the levels of cGMP of isolated pregnant rat myometrium

Abstract

This study was designed to compare the effects of YCA (3-(5-hydroxymethyl-2'-furyl)-1-benzyl indazole), a nitric oxide (NO)independent soluble guanylate cyclase activator, and diethylenetriamine-NONOate (DETA/NO), a NO donor, on spontaneous contractions and the levels of cyclic GMP (cGMP) of myometrial strips isolated from timed-pregnant rats. Myometrial strips were obtained from timed-pregnant Wistar albino rats (n = 10) and were mounted in organ baths and tested for changes in isometric tension in response to YC-1 and DETA/NO. We also evaluated the effect of YC-1 and DETA/NO on the levels of cGMP in myometrial strips obtained from timed-pregnant rat uterine horns (n = 20). YC-1 (10(-9)-3 x 10(-5) M) and DETA/NO (10(-7) -10(-4) M) concentration-dependently decreased the amplitude and frequency of spontaneous contractions of myometrial strips isolated from term-pregnant rats. The inhibitions of the amplitude and frequency of spontaneous contractions by YC-1 and DETA/NO were antagonized with methylene-blue (10-5 M). Antagonistic effect of methylene-blue (10-5 M) was more on DETA/NO responses than that of YCA (P < 0.05). In addition, YC-l-stimulated myometrial strips showed more elevation in myometrial cGMP than that of DETA/NO (P < 0.05). We demonstrated that YC-l and DETA/NO induce relaxations in the amplitude and frequency of spontaneous contractions of myometrial strips with different potencies. We also found that YC-l and DETA/NO-induced relaxations are associated with significant increases in cGMP. These results might suggest that the relaxant effects of YC-l and DETA/NO on the rat myometrium could be due to the stimulation of the soluble guanylate cyclase and cGMP may play a role for the maintenance of uterine quiescence during pregnancy. (c) 2005 Published by Elsevier B.V.