Nitric Oxide mediates various biological phenomena, including vascular smooth muscle relaxation. In the present study, we sought to determine if an L-arginine nitric oxide-relaxation system is present in the uterus and if it modulates contractility during pregnancy. The substrate and a donor of nitric oxide and nitric oxide gas caused substantial relaxation of the spontaneous contractility of tissues from the rat uterus in vitro during pregnancy. Inhibitors of nitric oxide synthase and soluble guanylate cyclase reversed the relaxation effects of L-arginine. Nitric oxide was produced by the uterus in organ culture. Relaxation effects of L-arginine on the pregnant rat uterus were diminished at the time of spontaneous labor and postpartum. Nitric oxide production was also substantially reduced during labor. These results show that an L-arginine-nitric oxide-relaxation system is present in the uterus and it inhibits contractility during pregnancy but not during labor.
Previously, we demonstrated the presence of an L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway in the rat uterus and that NO inhibits contractility during pregnancy but not during delivery. In the present study, we investigated the possible role of sex steroid hormones in the regulation of NO synthesis and cGMP generation. NO, measured as nitrite production, and cGMP were determined in full thickness uterine tissues from either pregnant rats on different gestational days or nonpregnant animals after treatment with steroid hormones. NO formation was low in tissues from nonpregnant rats, substantially increased during pregnancy and decreased during labor and immediately postpartum. The cGMP content in the same tissues followed a similar trend. Uterine nitrite production and cGMP levels from animals treated with estradiol and estradiol + progesterone were significantly lower compared to those treated with vehicle or progesterone. These data provide strong evidence that the NO-cGMP system is upregulated during pregnancy to maintain uterine quiescence and a rise in estrogen at term could inhibit this system and thus initiate labor.
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