Abstract
Women with renal disease progress at a slower rate to end stage renal disease than men. As angiotensin II has both hemodynamic and direct renal effects, we hypothesized that the female protection may result from gender differences in responses to angiotensin II. Therefore, we studied gender differences in response to angiotensin II, during acute (human) and chronic (rats) angiotensin II administration. In young healthy men (n = 18) and women (n = 18) we studied the responses of renal hemodynamics (125I-iothalamate and 131I-Hippuran) and blood pressure to graded angiotensin II infusion (0.3, 1.0, and 3.0 ng/kg/min for 1 h). Men had increased responses of diastolic blood pressure (P = 0.01), mean arterial pressure (P = 0.05), and a more pronounced decrease in effective renal plasma flow (P = 0.009) than women. We measured the changes in proteinuria and blood pressure in response to chronic administration (200 ng/kg/min for 3 weeks) of angiotensin II in rats. Male rats had an increased response of proteinuria compared with females (GEE analysis, P = 0.001). Male, but not female, angiotensin II-treated rats had increased numbers of renal interstitial macrophages compared to sham-treated rats (P < 0.001). In conclusion, gender differences are present in the response to acute and chronic infusion of angiotensin II. Difference in angiotensin II sensitivity could play a role in gender differences in progression of renal disease.
Highlights
Women generally have a lower risk for developing cardiovascular disease (CVD) and chronic kidney disease (CKD) than men
Men showed an increased blood pressure and effective renal plasma flow (ERPF) response, and a slightly decreased Glomerular filtration rate (GFR) response to acute angiotensin II (ang II) infusion compared with women
We showed that chronic ang II infusion resulted in a higher blood pressure in male compared with female rats, which confirms previous studies
Summary
Women generally have a lower risk for developing cardiovascular disease (CVD) and chronic kidney disease (CKD) than men. They progress slower to end stage renal disease (ESRD) after a renal insult (Silbiger and Neugarten 1995). Elucidation of gender differences is important, since this may translate into gender-specific treatment and subsequently to better outcomes in men and women The importance of such studies is supported by the evidence suggesting gender differences in the efficacy and effects of anti-hypertensive medication in general and in RAAS blockade
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