肥胖增强了 Zucker 大鼠肾循环中血管收缩剂对血管紧张素 II 的反应性。
Obesity augments vasoconstrictor reactivity to angiotensin II in the renal circulation of the Zucker rat.
作者信息
Stepp David W, Boesen Erika I, Sullivan Jennifer C, Mintz James D, Hair Clark D, Pollock David M
机构信息
Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd., Augusta, GA 30912, USA.
出版信息
Am J Physiol Heart Circ Physiol. 2007 Oct;293(4):H2537-42. doi: 10.1152/ajpheart.01081.2006. Epub 2007 Aug 10.
Obesity is an emerging risk factor for renal dysfunction, but the mechanisms are poorly understood. Obese patients show heightened renal vasodilation to blockade of the renin-angiotensin system, suggesting deficits in vascular responses to angiotensin II (ANG II). This study tested the hypothesis that obesity augments renal vasoconstriction to ANG II. Lean (LZR), prediabetic obese (OZR), and nonobese fructose-fed Zucker rats (FF-LZR) were studied to determine the effects of obesity and insulin resistance on reactivity of blood pressure and renal blood flow to vasoconstrictors. OZR showed enlargement of the kidneys, elevated urine output, increased sodium intake, and decreased plasma renin activity (PRA) vs. LZR, and renal vasoconstriction to ANG II was augmented in OZR. Renal reactivity to norepinephrine and mesenteric vascular reactivity to ANG II were similar between LZR and OZR. Insulin-resistant FF-LZR had normal reactivity to ANG II, indicating the insulin resistance was an unlikely explanation for the changes observed in OZR. Four weeks on a low-sodium diet (0.08%) to raise PRA reduced reactivity to ANG II in OZR back to normal levels without effect on LZR. From these data, we conclude that in the prediabetic stages of obesity, a decrease in PRA is observed in Zucker rats that may lead to increased renal vascular reactivity to ANG II. This increased reactivity to ANG II may explain the elevated renal vasodilator effects observed in obese humans and provide insight into early changes in renal function that predispose to nephropathy in later stages of the disease.
肥胖是肾功能障碍的一个新出现的风险因素,但其机制尚不清楚。肥胖患者对肾素-血管紧张素系统阻断的肾血管舒张增强,提示血管对血管紧张素II(ANG II)的反应存在缺陷。本研究检验了肥胖会增强肾血管对ANG II的收缩反应这一假说。对瘦素(LZR)、糖尿病前期肥胖(OZR)和非肥胖果糖喂养的 Zucker 大鼠(FF-LZR)进行研究,以确定肥胖和胰岛素抵抗对血压反应性以及肾血流对血管收缩剂反应性的影响。与LZR相比,OZR表现出肾脏增大、尿量增加、钠摄入量增加以及血浆肾素活性(PRA)降低,且OZR对ANG II的肾血管收缩增强。LZR和OZR之间对去甲肾上腺素的肾反应性以及对ANG II的肠系膜血管反应性相似。胰岛素抵抗的FF-LZR对ANG II具有正常反应性,表明胰岛素抵抗不太可能解释在OZR中观察到的变化。采用低钠饮食(0.08%)四周以提高PRA,可使OZR对ANG II的反应性恢复到正常水平,而对LZR无影响。根据这些数据,我们得出结论,在肥胖的糖尿病前期阶段,Zucker大鼠中观察到PRA降低,这可能导致肾血管对ANG II的反应性增加。这种对ANG II反应性的增加可能解释了在肥胖人群中观察到的肾血管舒张作用增强,并为疾病后期易患肾病的肾功能早期变化提供了见解。