Oral contraceptive administration aggravates nitric oxide synthesis inhibition-induced high blood pressure in female rats

Abstract

The use of estrogen–progestogen oral contraceptive (OC) is associated with high blood pressure, although mechanisms responsible are still unclear. This study sought to investigate the effects of administration of OC on high blood pressure resulting from nitric oxide (NO) synthesis inhibition in female Sprague– Dawley rats. Rats were given ethinyl estradiol in combination with norgestrel and were treated with NO synthase inhibitor, N G-nitro- l-arginine methyl ester ( l-NAME) in the drinking water or drinking water alone for 6 weeks. OC treatment alone led to a significant increase in blood pressure and positive water balance. Treatment with l-NAME alone resulted in a significant elevation of blood pressure without significant positive water balance. Concomitant treatment with OC and l-NAME produced significant increases in blood pressure and water balance. These magnitudes of increases were significantly greater than those observed in rats treated with OC or l-NAME alone. Treatment with OC did not affect NO biosynthesis with or without concurrent l-NAME treatment. Treatment with OC and/or l-NAME did not significantly affect body weight, food intake, heart rate, cardiac weight/body weight ratio, plasma sodium, glomerular filtration rate and urinary sodium output. Conclusion: These data demonstrate that OC administration resulted in a modest increased blood pressure via enhanced water retention that was not associated with impaired NO synthesis. On the other hand, these results showed that increased blood pressure induced by inhibition of NO synthesis was not associated with water retention. The study also indicated that OC administration aggravated increase in blood pressure during NO synthesis inhibition, via enhanced water retention.