Abstract Body: Introduction: Before menopause, women generally have lower rates of hypertension and cardiovascular events compared with men. After menopause, women lose significant cardiovascular and renal protection. Estrogen's effect on kidney function is controversial, with some studies showing protection and others, including ours, indicating long-term estrogen exposure causes renal damage. The relationship between estrogen, hypertension, and kidney function is still not fully understood. Aim: Our aim was to investigate the interaction between hypertension and menopause on kidney function and determine whether the timing of disease initiation, pre- or post-menopause, influences these effects. Methods: Female Long-Evans rats were ovariectomized at 46 weeks of age to simulate menopause and treated with estradiol (E2) or vehicle. Some groups were infused with angiotensin II (Ang; 700ng/kg/min), either 4 weeks before or at the time of ovariectomy. Blood pressure (BP), proteinuria, creatinine clearance, osmolality, glomerular (GLOM) area, GLOM collagen deposition, and GPER and ERα receptor by droplet digital PCR were assessed by two-way ANOVA. Results: BP was higher with Ang (P=0.003) but was not affected by E2 (P=0.85) or timing (P=0.49). E2 significantly increased kidney hypertrophy (P<0.001) independent of Ang (P=0.27), especially when hypertension was initiated at the time of menopause (P<0.001). Both E2 and Ang increased water intake and urine output (P<0.05), especially when hypertension was initiated at the time of menopause. Proteinuria, an indicator of renal damage, was significantly higher with E2 (P=0.03), Ang increased GLOM area (P<0.05) with no effect of E2. There was no change in the urinary osmolality due to either Ang or E2. GLOM collagen deposition was not different between groups. In the renal cortex, E2 decreased ERα mRNA (P<0.01), with no difference in GPER. Conclusion: Although E2 did not affect blood pressure, it worsened the impact of hypertension on kidney function, particularly when started at the time of ovariectomy. This may be due to decreased ERα in the cortex and likely unrelated to damage in the glomerulus.
Keywords: Menopause, hypertension, renal damage