Effects of estrogen in the regulation of nitric oxide pathway during development of hypertension in rats.

A down-regulation of nitric oxide (NO) synthesis has been involved in the genesis of cardiovascular complications associated with hypertension. This study was designed to assess the role of estrogen in the modulation of the pressor response elicited by N-methyl-L-arginine (L-NMA) in conscious spontaneously hypertensive (SHR) rats before and after ovariectomy. Four-week-old female SHR (n = 6) and age matched Wistar-Kyoto (WKY; control n = 7) rats were treated with mestranol (50 micrograms/100 g BW) twice a week for 8 weeks. At week 12, SHR and WKY were instrumented with catheters in the femoral artery and vein. L-NMA (30 mg/kg, i.v.) was infused over 1 min in SHR and WKY rats prior to and 3 weeks following ovariectomy. Results were compared to control rats, non-estrogen treated female SHR (n = 6) and WKY (n = 6). Our data show that the pressor response induced by L-NMA in estrogen-treated SHR was similar to estrogen-treated WKY (29 +/- 4 vs 25 +/- 2 mmHg). As compared to intact SHR and WKY, our data demonstrate that 3 weeks following ovariectomy, baseline blood pressure increased by 15% in SHR but remained unchanged in ovariectomized WKY. Furthermore, the magnitude of the L-NMA-induced pressor effect was significantly decreased in ovariectomized SHR and WKY. Our data support the concept that estrogen treatment does not play a significant role in the modulation of NO pathway in female SHR, whereas the presence of an intact ovaria modulates the NO pathway in female WKY.