17β-Estradiol deficiency reduces potassium excretion in an angiotensin type 1 receptor-dependent manner

This study examined the effects of ovariectomy (OVX) and 17β-estradiol (E 2 ) replacement (OVX + E 2 ) on renal function in Sprague-Dawley rats. OVX caused a 40% decrease in the fractional excretion of potassium (FE K + ) that was prevented by E 2 replacement [Sham, 24.2 ± 2.9%; OVX, 14.5 ± 2.1% ( P < 0.05 vs. OVX + E 2 ); and OVX + E 2 , 26.2 ± 2.7%; n = 7–11] and that corresponded to significant increases in plasma potassium [(in mmol/l): Sham, 3.15 ± 0.087; OVX, 3.42 ± 0.048 ( P < 0.05 vs. OVX + E 2 ); and OVX + E 2 , 3.19 ± 0.11; n = 7–11]. No effects of OVX were detected on plasma levels of sodium and aldosterone. Angiotensin II type 1 receptor (AT 1 R) densities in ovariectomized rats were 1.4-fold and 1.3-fold higher in glomerular [maximum binding capacity (B max ; in fmol/mg protein): Sham, 482 ± 21; OVX, 666 ± 20 ( P < 0.05 vs. OVX + E 2 ); and OVX + E 2 , 504 ± 26; n = 7–11] and proximal tubular [B max (in fmol/mg protein): Sham, 721 ± 16; OVX, 741 ± 24 ( P < 0.05 vs. OVX + E 2 ); and OVX + E 2 , 569 ± 23; n = 7–11] membranes compared with E 2 replete animals, respectively. Both the angiotensin-converting enzyme inhibitor captopril and the AT 1 R antagonist losartan prevented the OVX-induced decrease in the FE K + and the increase in renal AT 1 R densities, suggesting that E 2 deficiency reduces potassium excretion in an ANG II/AT 1 R-dependent manner. These findings may have implications for renal function in postmenopausal women as well as contribute to the reasons underlying the age-induced increase in susceptibility to hypertension-associated disease in women.