Effect of changes in nitric level oxide on myometrial contractility in pregnant and non-pregnant rats

ABSTRACT

Nitric oxide [NO] has been recognized as a molecule that shares in regulation of the reproductive system physiology. The present study aimed to investigate the effects of NO excess and NO deficiency on spontaneous myometrial contractions and on myometrial responsiveness to oxytocin as well, in both non-pregnant and late pregnant rats. Female adult rats were divided into two main groups estrogen-primed non-pregnant model and time-mated late pregnant model. Rats in each model were divided into three groups a control group, L-arginine-treated group and L-NAME-treated group. Myometrial strips taken from the different groups were suspended in organ bath containing Krebs' solution, gassed with 95% O2 and 5% CO2 for recording of isometric contractions. Spontaneous uterine motility was recorded, followed by oxytocin addition for recording of myometrial responsiveness to this hormone. Serum nitrate level was determined in all rats. L-arginine supplementation caused a significant increase in serum nitrate levels in both rat models, accompanied by decreased spontaneous myometrial contractility and attenuation of the stimulatory effect of oxytocin in both non-pregnant and pregnant rats, compared to the control values. The predominating effect in the non-pregnant model was on the average force, and in the pregnant model on the frequency of contraction. Following treatment with L-NAME. serum nitrate was significantly decreased, yet the spontaneous myometrial contractility and its responsiveness to oxytocin were non-significantly changed in both non-pregnant and pregnant rats, compared to the control group. The NO donor L-arginine has proved to have an inhibitory effect on both spontaneous and oxytocin-induced myometrial contractions, when administered in vivo, in both non-pregnant and late pregnant states, establishing the importance of the L-arginine/NO system as a uterine smooth muscle relaxant. L-arginine could, therefore, provide a useful therapeutic measure for conditions with pathological uterine contractility, like dysmenorrhea or preterm labor, taking into consideration that increased NO attenuates myometrial responsiveness to oxytocin