Transgenic rats carrying the mouse Ren-2 gene (Ren-2d) 27 provide a unique model to study the interplay between the renin-angiotensin system and estrogen in the pathogenesis of hypertension. In this study we measured the effects of ovariectomy and estrogen replacement on blood pressure and the contribution of vascular endothelium relaxing factor, nitric oxide, in female transgenic hypertensive rats and normotensive Sprague Dawley (SD) rats. Both groups of animals were either ovariectomized or sham operated at 12 weeks of age. Ovariectomized rats were treated with either 17ßestradiol (70 |xg/day) or placebo for 4 weeks, whereas sham operated rats received placebo alone. Mean arterial blood pressure measured in conscious rats directly by an arterial catheter was significantly higher in ovariectomized rats, compared with ovariectomized rats given estrogen replacement therapy for both transgenic (167 ± 5 v 154 ± 4 mm Hg, P < .05) and SD rats (125 ± 4 v 113 ± 5 mm Hg, P < .05). The contribution of endothelium-derived nitric oxide to the maintenance of blood pressure was examined by acute systemic injection of NG-monomethyl-L-arginine (L-NMMA, 10 mg/kg). L-NMMA caused a significantly greater increase in blood pressure in sham-operated trans- genic as compared to SD rats (34 ± 3 v 14 ± 3 mm Hg,P .05). The response in ovariectomized transgenic rats was markedly reduced (13 ± 3 mm Hg), reaching levels that were no different from sham-operated SD rats. Estrogen replacement in ovariectomized transgenic rats returned the re sponse to L-NMMA to levels (22 ± 6 mm Hg) not significantly different from the sham-operated transgenic rats. In SD rats neither ovariectomy nor estrogen replacement therapy had any effect on the pressor response produced by L-NMMA. These studies indicate that estrogen countermodulates the renin-mediated hypertension in transgenic rats by enhancing the activity of endothelial-derived relaxing factors. Am J Hypertens 1994;7:576-582
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Brosnihan et al. (1994) studied this question.