McKoy, Marsha-Lyn G.; Simon, Oswald R.
Author Affiliation, Ana.
Department of Basic Medical Sciences
The effects of SIN-1 on contractility and cyclic GMP levels in the pregnant mouse uterus
Proceedings of the Western Pharmacology Society
Date of Publication
Nitric oxide (NO) is accepted as a mediator of relaxation in various smooth muscles. It is synthesized endogenously from L-arginine by nitric oxide synthase (NOS), which exists as several isoforms. The established mechanism of action of NO in vascular and some non-vascular smooth muscles is activation of guanylate cyclase, leading to increaed intracellular levls of cyclic GMP, which relaxes the smooth muscle. There are conflicting reports surrounding the existence of this NO-guanylate cyclase-cyclic GMP relaxation pathway in the myometrium. Reports from several studies gave evidence for the operation of this system in the pregnant rat [2,4] and in human [2,5] myometria. It was proposed from these studies that this system modulates uterine contractility and may be involved in maintaining uterine quiescence during pregnancy. However, other studies involving several NO donors indicated a lack of correlation between elevations in cyclic GMP levels and myometrial relaxation . This was further supported by investigations in which the use of guanylate cyclase inhibitors blocked elevations in cyclic GMP levels without inhibiting the relevant effects of NO donors on uterine contractions in the rat , guinea-pig , monkey  and human . This experiment was designed to investigate the effects of the NO donor, 3-morpholinosydnonimine (SIN-1), on modulation of agonist-evoked contractions in the pregnant mouse and to determine whether these effects are dependent on changes in cyclic GMP levels.....