There seem to be gender differences in the function of the renin-angiotensin system (RAS). Do such differences also exist in the response to RAS blockade?OBJECTIVE
To compare the hemodynamic changes and reduction in angiotensin II sensitivity elicited by an angiotensin receptor blocker (ARB) in healthy men and women.DESIGN AND INTERVENTION
The study recruited healthy, nonobese nonsmokers with normal blood pressure who were not taking any regular medications. Participants were requested to avoid caffeine for 12 h before entering the study, and to follow a protein-controlled and sodium-controlled diet for 1 week before each phase of the study. At baseline, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined before and after an infusion of 3 ng/kg/min angiotensin II by measuring clearance of inulin and para-aminohippurate. Mean arterial pressure (MAP) was recorded every 30 min throughout. The procedure was repeated fortnightly, with participants receiving irbesartan at doses of 75 mg/day for 4 weeks and 150 mg/day for the subsequent 4 weeks. Blood samples were obtained before infusion for quantification of renin, angiotensin II and hematocrit.OUTCOME MEASURES
MAP, GFR, ERPF, renal blood flow (RBF; ERPF ÷ [1 − hematocrit]), renal vascular resistance (RVR; MAP ÷ RBF) and filtration fraction (ratio of GFR:ERPF) were recorded before and after angiotensin II infusion. Plasma renin and angiotensin II levels were also analyzed.RESULTS
At baseline, there were no significant differences in age, BMI, plasma angiotensin II level or plasma renin level between the 15 men and 15 women recruited (mean ages 27 years and 28 years, respectively); however, baseline MAP was significantly higher in men (83 mmHg vs 77 mmHg; P<0.05). MAP and RVR declined substantially and comparably in the two groups during irbesartan treatment. None of GFR, ERPF, filtration fraction or RBF changed significantly in either group during the study. Plasma renin and angiotensin II levels were significantly lower in men than in women when measured after 4 weeks of irbesartan 75 mg and after 2 weeks of irbesartan 150 mg (P=0.04 for difference in angiotensin II levels after 4 weeks of irbesartan 75 mg; P=0.02 for all other comparisons). Before irbesartan treatment, men and women had similar responses to angiotensin II infusion in terms of MAP, GFR, ERPF, RBF, RVR and filtration fraction. After treatment, men had significantly smaller reductions than women in the MAP response (from 2 weeks of irbesartan 75 mg onward), ERPF response, RBF response, filtration fraction response and RVR response (all from 4 weeks of irbesartan 75 mg onward; P<0.05 for all). The pressor response to angiotensin II was abolished in women after 2 weeks of receiving irbesartan 75 mg, but remained at 12 mmHg in men at the end of the study. No significant changes in the GFR response to angiotensin II occurred in either group.CONCLUSION
Men have different renal hemodynamic responses to RAS blockers compared with women.