Lohmeier T E, Yang H M
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505.
Hypertension. 1991 Mar;17(3):278-87. doi: 10.1161/01.hyp.17.3.278.
The purpose of the present study was to determine the role of angiotensin II (Ang II) in mediating renal responses to chronic intrarenal norepinephrine infusion. Norepinephrine was continuously infused for 5 days into the renal artery of unilaterally nephrectomized dogs at progressively higher daily infusion rates: 0.05, 0.10, 0.20, 0.30, and 0.40 micrograms/kg/min. In three additional groups of dogs, norepinephrine infusion was repeated during chronic intravenous captopril administration to fix plasma Ang II concentration at 1) low levels (no Ang II infused), 2) high levels in the renal circulation (Ang II infused intrarenally at a rate of 1 ng/kg/min), and 3) high levels in the systemic circulation (Ang II infused intravenously at a rate of 5 ng/kg/min). In the control group of animals with intact renin-angiotensin systems, there were progressive increments in mean arterial pressure (from 96 +/- 4 to 141 +/- 6 mm Hg) and plasma renin activity (from 0.4 +/- 0.1 to 10.9 +/- 4.5 ng angiotensin I/ml/hr) and concomitant reductions in glomerular filtration rate and renal plasma flow to approximately 40% of control during the 5-day norepinephrine infusion period. In marked contrast, when captopril was infused chronically without Ang II, mean arterial pressure was 20-25 mm Hg less than that under control conditions, and the renal hemodynamic effects of norepinephrine were greatly exaggerated; by day 3 of norepinephrine infusion, both glomerular filtration rate (16 +/- 2% of control) and renal plasma flow (12 +/- 4% of control) were considerably lower than values in control animals (86 +/- 4% and 80 +/- 8% of control, respectively). Similarly, when a high level of Ang II was localized in the renal circulation during captopril administration, mean arterial pressure was depressed, and again there were pronounced renal responses to norepinephrine. Conversely, when Ang II was infused intravenously during captopril administration, mean arterial pressure was not reduced, and the glomerular filtration rate and renal plasma flow responses to norepinephrine were similar to those that occurred under control conditions. These findings indicate that the renin-angiotensin system prevents exaggerated renal vascular responses to chronic norepinephrine stimulation by preserving renal perfusion pressure.
本研究的目的是确定血管紧张素II（Ang II）在介导肾脏对慢性肾内去甲肾上腺素输注反应中的作用。将去甲肾上腺素以逐渐升高的每日输注速率（0.05、0.10、0.20、0.30和0.40微克/千克/分钟）连续5天输注到单侧肾切除犬的肾动脉中。在另外三组犬中，在慢性静脉注射卡托普利期间重复输注去甲肾上腺素，以将血浆Ang II浓度固定在：1）低水平（未输注Ang II），2）肾循环中的高水平（以1纳克/千克/分钟的速率肾内输注Ang II），以及3）体循环中的高水平（以5纳克/千克/分钟的速率静脉输注Ang II）。在肾素-血管紧张素系统完整的动物对照组中，在5天的去甲肾上腺素输注期间，平均动脉压（从96±4毫米汞柱升至141±6毫米汞柱）和血浆肾素活性（从0.4±0.1纳克血管紧张素I/毫升/小时升至10.9±4.5纳克血管紧张素I/毫升/小时）逐渐升高，同时肾小球滤过率和肾血浆流量降至对照组的约40%。与之形成鲜明对比的是，在无Ang II的情况下长期输注卡托普利时，平均动脉压比对照条件下低20 - 25毫米汞柱，并且去甲肾上腺素的肾血流动力学效应被极大地放大；在去甲肾上腺素输注的第3天，肾小球滤过率（对照组的16±2%）和肾血浆流量（对照组的12±4%）均显著低于对照动物的值（分别为对照组的86±4%和80±8%）。同样，当在卡托普利给药期间肾循环中存在高水平的Ang II时，平均动脉压降低，并且对去甲肾上腺素再次出现明显的肾脏反应。相反，当在卡托普利给药期间静脉输注Ang II时，平均动脉压未降低，并且肾小球滤过率和肾血浆流量对去甲肾上腺素的反应与对照条件下相似。这些发现表明，肾素-血管紧张素系统通过维持肾灌注压来防止对慢性去甲肾上腺素刺激的过度肾血管反应。
