Impact of gender on the renal response to angiotensin II

Background. It is clear that women with renal disease progress to end stage at a slower rate than do men. We hypothesized that this protection may result from gender-mediated differences in responses to angiotensin II (Ang II), which has known hemodynamic effects that are thought to promote renal disease progression. We examined sex differences in renin-angiotensin system (RAS) function by measuring renal hemodynamic function and circulating plasma components of the RAS at baseline and in response to graded infusions of Ang II. Methods. We studied two groups of normal healthy subjects, 24 men and 24 women, mean age 28 +/- 1 years, ingesting a controlled sodium and protein diet. We examined baseline concentrations of angiotensin converting enzyme, plasma renin activity, Ang II, and aldosterone. Inulin and paraaminohippurate clearance techniques were used to estimate effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) at baseline and in response to graded Ang II infusion (0.5, 1.5, and 2.5 ng/kg/min). Results. Mean baseline values for mean arterial pressure and aldosterone were lower in women, whereas values for plasma Ang II, GFR, ERPF, and filtration fraction (FF) did not differ. In response to Ang II, both groups exhibited a similar increase in mean arterial pressure and a decline in ERPF. GFR was maintained during Ang II infusion only in men, resulting in an augmentation of FF. In women, GFR declined in parallel with ERPF, and the FF response was significantly blunted. 17 beta-Estradiol plasma concentrations influenced the ERPF response to Ang II infusion, with higher levels predicting a blunting of the decrease. The GFR response was not affected. Conclusions. The renal microcirculation in sodium-replete women may respond differently to Ang II than that of men, with the female sex predicting a lesser augmentation of FF and possibly a blunted increase in intraglomerular pressure. The mechanism remains obscure, but these contrasting responses may help to explain gender-mediated differences in renal disease progression.