Miller J A, Anacta L A, Cattran D C
Department of Medicine, University of Toronto, Toronto, Canada.
Kidney Int. 1999 Jan;55(1):278-85. doi: 10.1046/j.1523-1755.1999.00260.x.
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.
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).
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. 17beta-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.
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.
很明显，患有肾脏疾病的女性进展到终末期的速度比男性慢。我们推测这种保护作用可能源于性别介导的对血管紧张素II（Ang II）反应的差异，已知Ang II具有血流动力学效应，被认为会促进肾脏疾病的进展。我们通过测量基线时以及对不同剂量Ang II输注的反应时的肾脏血流动力学功能和肾素 - 血管紧张素系统（RAS）的循环血浆成分，来研究RAS功能的性别差异。
我们研究了两组正常健康受试者，24名男性和24名女性，平均年龄28±1岁，摄入控制钠和蛋白质的饮食。我们检测了血管紧张素转换酶、血浆肾素活性、Ang II和醛固酮的基线浓度。使用菊粉和对氨基马尿酸清除技术来估计基线时以及对不同剂量Ang II输注（0.5、1.5和2.5 ng/kg/min）的反应时的有效肾血浆流量（ERPF）和肾小球滤过率（GFR）。
女性的平均动脉压和醛固酮的平均基线值较低，而血浆Ang II、GFR、ERPF和滤过分数（FF）的值没有差异。对Ang II的反应中，两组的平均动脉压均有相似的升高，ERPF均下降。仅在男性中，Ang II输注期间GFR得以维持，导致FF增加。在女性中，GFR与ERPF平行下降，且FF反应明显减弱。血浆17β - 雌二醇浓度影响ERPF对Ang II输注的反应，浓度越高，预测下降的减弱越明显。GFR反应不受影响。
钠充足的女性的肾脏微循环对Ang II的反应可能与男性不同，女性预示着FF增加较少，肾小球内压升高可能减弱。机制尚不清楚，但这些不同的反应可能有助于解释肾脏疾病进展中的性别介导差异。
