Nematbakhsh Mehdi, Safari Tahereh
Water and Electrolytes Research Center, Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran.
Gen Physiol Biophys. 2014;33(3):365-72. doi: 10.4149/gpb_2014008. Epub 2014 Jun 26.
Epidemiologic and clinical studies have shown that progression of renal disease in male is faster than that in female. However, the exact mechanisms are not well recognized. Angiotensin (1-7) (Ang 1-7) receptor, called "Mas", is an element in the depressor arm of renin angiotensin system (RAS), and its expression is enhanced in females. We test the hypothesis that Mas receptor (MasR) blockade (A779) attenuates renal blood flow (RBF) in response to infusion of graded doses of Ang 1-7 in female rats. Male and female Wistar rats were anesthetized and catheterized. Then, the mean arterial pressure (MAP), RBF, and controlled renal perfusion pressure (RPP) responses to infusion of graded doses of Ang 1-7 (100-1000 ng/kg/min i.v.) with and without A779 were measured in the animals. Basal MAP, RPP, RBF, and renal vascular resistance (RVR) were not significantly different between the two groups. After Ang 1-7 administration, RPP was controlled at a constant level. However, RBF increased in a dose-related manner in response to Ang 1-7 infusion in both male and female rats (Pdose<0.0001), but masR blockade significantly attenuated this response only in female (Pgroup=0.04) and not male (Pgroup=0.23). In addition, A779 increased the RBF response to Ang 1-7 to a greater extent. This is while the increase in male was not significant when compared with that in female (Pgender=0.08). RVR response to Ang 1-7 was insignificantly attenuated by A779 in both genders. The masR differently regulated RBF response to Ang 1-7 in the two genders, and the effect was greater in female rats. The masR may be a target for improvement of kidney circulation in renal diseases.
流行病学和临床研究表明，男性肾脏疾病的进展比女性更快。然而，确切机制尚未完全明确。血管紧张素（1-7）（Ang 1-7）受体，即“Mas”，是肾素血管紧张素系统（RAS）降压分支中的一个元件，其表达在女性中增强。我们检验了这样一个假设：在雌性大鼠中，Mas受体（MasR）阻断剂（A779）可减弱对不同剂量Ang 1-7输注的肾血流量（RBF）反应。将雄性和雌性Wistar大鼠麻醉并插管。然后，在动物中测量给予和不给予A779时，对不同剂量Ang 1-7（100 - 1000 ng/kg/min静脉注射）输注的平均动脉压（MAP）、RBF和可控肾灌注压（RPP）反应。两组之间的基础MAP、RPP、RBF和肾血管阻力（RVR）无显著差异。给予Ang 1-7后，RPP被控制在恒定水平。然而，在雄性和雌性大鼠中，RBF均以剂量相关的方式随Ang 1-7输注而增加（P剂量<0.0001），但MasR阻断仅在雌性中显著减弱了这种反应（P组=0.04），而在雄性中未减弱（P组=0.23）。此外，A779在更大程度上增加了对Ang 1-7的RBF反应。与雌性相比，雄性的增加不显著（P性别=0.08）。A779在两性中对Ang 1-7的RVR反应减弱均不显著。MasR对两性中Ang 1-7的RBF反应调节不同，且在雌性大鼠中作用更大。MasR可能是改善肾脏疾病肾循环的一个靶点。
