12874087

pubmed:Citation

4

The influence of estrogen on the regulation of cardiovascular function remains a controversial and complex area of investigation. We assessed the effects of estrogen depletion in the congenic mRen(2). Lewis rat, established from the back-cross of the original (mRen2)-27 transgenic onto the Lewis inbred strain. Ovariectomy of heterozygous mRen(2). Lewis at 4 to 5 weeks resulted in a progressive increase in blood pressure compared with the sham surgery congenics at weeks 6 to 11. At 11 weeks, the ovariectomized mRen(2). Lewis (OVX) systolic blood pressure averaged 195+/-3.7 mm Hg versus 141+/-4.0 mm Hg for sham. Plasma Angiotensin (Ang) II, serum ACE activity, plasma renin concentration, as well as urinary excretion of Ang II, 8-isoprostane F2alpha, and endothelin-1 were elevated; however, renal mRNA levels of eNOS were suppressed after ovariectomy. Estrogen replacement reduced blood pressure below both the sham and OVX by 11 weeks (125+/-2.9 mm Hg, n=7, P<0.01 versus OVX and sham). Moreover, the AT1 receptor antagonist olmesartan (CS866; week 12 to 16) essentially normalized blood pressure to 113+/-5.4 mm Hg (n=6, P<0.01 versus OVX and sham). The attenuation of the hypertension was still evident 7 weeks after complete withdrawal of treatment (124+/-4.1 mm Hg at week 23). In summary, the OVX mRen.2. Lewis exhibited a rapid and sustained increase in blood pressure. Estrogen or olmesartan lowered pressure by a similar extent. We conclude that the ovary exerts considerable influence on the regulation of the blood pressure in the mRen2. Lewis strain, possibly by limiting activation of the renin-angiotensin system.

eng

IM

MEDLINE

1524-4563

Electronic

NLM

781-6

pubmed-meshheading:12874087-Angiotensin Receptor Antagonists, pubmed-meshheading:12874087-Animals, pubmed-meshheading:12874087-Animals, Congenic, pubmed-meshheading:12874087-Blood Pressure, pubmed-meshheading:12874087-Dinoprost, pubmed-meshheading:12874087-Disease Progression, pubmed-meshheading:12874087-Endothelin-1, pubmed-meshheading:12874087-Estradiol, pubmed-meshheading:12874087-F2-Isoprostanes, pubmed-meshheading:12874087-Female, pubmed-meshheading:12874087-Hypertension, pubmed-meshheading:12874087-Imidazoles, pubmed-meshheading:12874087-Male, pubmed-meshheading:12874087-Mice, pubmed-meshheading:12874087-Ovariectomy, pubmed-meshheading:12874087-Rats, pubmed-meshheading:12874087-Rats, Inbred Lew, pubmed-meshheading:12874087-Receptor, Angiotensin, Type 1, pubmed-meshheading:12874087-Renin, pubmed-meshheading:12874087-Renin-Angiotensin System, pubmed-meshheading:12874087-Tetrazoles

Estrogen or the AT1 antagonist olmesartan reverses the development of profound hypertension in the congenic mRen2. Lewis rat.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't