Evidence suggests that gender differences exist in renin-angiotensin system (RAS) function. It was hypothesized that women may differ also in their response to RAS blockade. The renal and peripheral hemodynamic responses to incremental dosages of an angiotensin receptor blocker and the degree of angiotensin II (AngII) insensitivity achieved during 8 wk were examined in men and women. Participants were 30 young healthy men (n = 15; mean age 27 +/- 2) and women (n = 15; mean age 28 +/- 2) who were on a controlled sodium and protein diet for 1 wk before each study. The humoral, renal, and systemic response to incremental dosages of irbesartan (75 mg for 4 wk, then 150 mg for 4 wk) was assessed, as was the pressor response to AngII (3 ng/kg per min), at 2-wk intervals. AngII type 1 receptor expression in skin biopsies was assessed at baseline and after 8 wk by a real-time PCR protocol. Men and women both exhibited significant declines in BP. Women achieved significantly reduced AngII sensitivity compared with men at lower dosages, showing no pressor response at 4 wk of 75 mg/d irbesartan, whereas men continued to exhibit a pressor response at 4 wk of 150 mg/d. Receptor expression at baseline did not differ between men and women but by 8 wk was significantly decreased in women and unchanged in men. Our findings indicate that men may require larger dosages of angiotensin receptor blocker than do women and that the BP response cannot be used as a surrogate marker for adequate RAS blockade of the renal microvasculature.

译文

:证据表明,肾素-血管紧张素系统(RAS)功能存在性别差异。据推测,妇女对RAS阻滞的反应也可能有所不同。在男性和女性中,检查了在8周内达到的肾血管和外周血流动力学对血管紧张素受体阻滞剂递增剂量的反应以及血管紧张素II(AngII)不敏感的程度。参加研究的是30名年轻健康男性(n = 15;平均年龄27/2)和女性(n = 15;平均年龄28/2),他们在每次研究前均接受钠和蛋白质的控制饮食1周。评估了对依贝沙坦递增剂量的体液,肾脏和全身反应(75 mg,4 wk,然后150 mg,4 wk),以及在2周时对AngII的升压反应(3 ng / kg / min)。间隔。在基线和8周后通过实时PCR方案评估皮肤活检中AngII 1型受体的表达。男性和女性的血压均显着下降。与较低剂量的男性相比,女性的AngII敏感性大大降低,厄贝沙坦在4 wk时未显示升压反应,而在150 mg / d的4 wk时,男性仍表现出升压反应。男性和女性在基线时的受体表达没有差异,但女性8周时显着降低,男性则保持不变。我们的发现表明,与女性相比,男性可能需要更大剂量的血管紧张素受体阻滞剂,并且BP反应不能用作肾微血管系统RAS充分阻断的替代指标。

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