title: Estrogen or the AT1 antagonist olmesartan reverses the development of profound hypertension in the congenic mRen2. Lewis rat.
abstract: 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.
authors.affiliation: Hypertension and Vascular Disease Center, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157-1095, USA. mchappel@wfubmc.edu
authors.forename: Mark C
authors.initials: MC
authors.lastname: Chappell
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Gallagher
authors.forename: David B
authors.initials: DB
authors.lastname: Averill
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Ferrario
authors.forename: K Bridget
authors.initials: KB
authors.lastname: Brosnihan
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D020296:Animals, Congenic; D001794:Blood Pressure / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives*; D018450:Disease Progression; D019332:Endothelin-1 / Q000378:metabolism; D004958:Estradiol / Q000627:therapeutic use*; D028441:F2-Isoprostanes / Q000378:metabolism; D005260:Female; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D000068557:Olmesartan Medoxomil; D010052:Ovariectomy; D051381:Rats; D011917:Rats, Inbred Lew; D044140:Receptor, Angiotensin, Type 1; D012083:Renin / Q000235:genetics*; D012084:Renin-Angiotensin System; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D057911:Angiotensin Receptor Antagonists; D019332:Endothelin-1; D028441:F2-Isoprostanes; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; C473112:Ren2 protein, mouse; D013777:Tetrazoles; C075750:8-epi-prostaglandin F2alpha; D004958:Estradiol; D000068557:Olmesartan Medoxomil; D015237:Dinoprost; D012083:Renin