Estrogen and salt sensitivity in the female mRen(2). Lewis rat.
The present study determined whether early loss of estrogen influences salt-sensitive changes in blood pressure, renal injury, and cardiac hypertrophy as well as the effects on the circulating renin-angiotensin-aldosterone system (RAAS) in the hypertensive female mRen(2). Lewis strain. Ovariectomy (OVX) of heterozygous mRen(2). Lewis rats on a normal salt (NS) diet (0.5% sodium) increased systolic blood pressure from 137+/-3 to 177+/-5 mmHg (P<0.01) by 15 wk but did not show any changes in cardiac-to-body weight index (CI), proteinuria, or creatinine clearance. Maintenance with a high-sodium (HS) diet (4%) increased blood pressure (203+/-4 mmHg, P<0.01), proteinuria (3.5+/-0.3 vs. 6.4+/-0.7 mg/day, P<0.05), and CI (4.0+/-0.1 vs. 5.2+/-0.1 mg/kg, P<0.01) but decreased creatinine clearance (0.89+/-0.15 vs. 0.54+/-0.06 ml/min, P<0.05). OVX exacerbated the effects of salt on the degree of hypertension (230+/-5 mmHg), CI (5.6+/-0.2 mg/kg), and proteinuria (13+/-3.0 mg/day). OVX increased the urinary excretion of aldosterone approximately twofold in animals on the NS diet (3.8+/-0.5 vs. 6.6+/-0.5 ng.mg creatinine-1.day-1, P<0.05) and HS diet (1.4+/-0.2 vs. 4.5+/-1.0 ng.mg creatinine-1.day-1, P<0.05). Circulating renin, angiotensin-converting enzyme, and angiotensin II were also significantly increased in the OVX group fed a HS diet. These results reveal that the protective effects of estrogen apart from the increase in blood pressure were only manifested in the setting of a chronic HS diet and suggest that the underlying sodium status may have an important influence on the overall effect of reduced estrogen.
Chappell
Mark C
MC
Hypertension and Vascular Disease Center, Wake Forest Univ. Health Sciences, Medical Center Blvd., Winston-Salem, North Carolina 27157-1095, USA. mchappel@wfubmc.edu
Yamaleyeva
Liliya M
LM
Westwood
Brian M
BM
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology*; D007674:Kidney Diseases / Q000209:etiology / Q000503:physiopathology; D010052:Ovariectomy; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D051381:Rats; D011917:Rats, Inbred Lew; D012083:Renin / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000009:adverse effects* / Q000494:pharmacology
D004967:Estrogens; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; D000450:Aldosterone; D007703:Peptidyl-Dipeptidase A; D012083:Renin