Estrogen and salt sensitivity in the female mRen(2).Lewis rat

Abstract

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.