Estrogen augments the contribution of nitric oxide to blood pressure regulation in transgenic hypertensive rats expressing the mouse Ren-2 gene.
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 17 beta-estradiol (70 micrograms/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 transgenic 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Brosnihan
K B
KB
Hypertension Center, Bowman Gray School of Medicine of Wake Forest University, Winston Salem, North Carolina 27157.
Moriguchi
A
A
Nakamoto
H
H
Dean
R H
RH
Ganten
D
D
Ferrario
C M
CM
D000818:Animals; D030801:Animals, Genetically Modified; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics*; D019323:omega-N-Methylarginine
D004967:Estrogens; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D012083:Renin