Carroll J F, Mizelle H L, Cockrell K, Reckelhoff J F, Clower B R, Granger J P
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Am J Physiol. 1997 Mar;272(3 Pt 2):R940-7. doi: 10.1152/ajpregu.1997.272.3.R940.
Aortic ring studies have demonstrated a decrease in endothelium-dependent relaxation or an enhanced response to vasoconstrictors in rabbits fed a high-cholesterol diet. Whether such abnormalities exist in the renal circulation is unclear. The purpose of this study was to determine functional renal responses to acetylcholine (ACh) or angiotensin II (ANG II) infusion in anesthetized rabbits after 8-10 wk of either a control diet (ACh, n = 6; ANG II, n = 6) or a 1% cholesterol diet (ACh, n = 7; ANG II, n = 7). Mean arterial pressure (MAP), renal blood flow (RBF), and glomerular filtration rate (GFR) were measured. Renal vascular resistance (RVR) was calculated as MAP/RBF. For ANG II experiments, captopril (15 microg x kg(-1) x min(-1)) was infused to suppress endogenous ANG II production. After two control clearance periods, either ACh (1 microg x kg(-1) x min(-1)) or ANG II (0.5 ng x kg(-1) x min(-1)) was infused into the renal artery; RBF was allowed to stabilize before experimental clearances. RBF increased with ACh (control: 25 +/- 2 to 39 +/- 2 ml/min; cholesterol: 26 +/- 2 to 40 +/- 3 ml/min) and decreased with ANG II infusions (control: 40 +/- 4 to 25 +/- 3 ml/min; cholesterol: 36 +/- 3 to 24 +/- 2 ml/min). Nitrate/nitrite excretion also increased with ACh infusion (control: 2.3 +/- 1.0 to 5.2 +/- 1.8 nmol x kg(-1) x min(-1); cholesterol: 2.3 +/- 0.3 to 6.0 +/- 1.3 nmol x kg(-1) x min(-1)). However, there were no significant differences between control and cholesterol groups in either response. GFR was unaltered during ACh and ANG II infusions. MAP, RVR, and urinary sodium and potassium excretion did not differ between groups in response to either drug. These results suggest that, despite significant hypercholesterolemia and large-vessel atherosclerosis, both nitric oxideinduced vasodilation and endothelium-dependent modulation of ANG II vasoconstriction in the renal circulation are unaffected by cholesterol feeding.
主动脉环研究表明，喂食高胆固醇饮食的兔子，其内皮依赖性舒张功能降低或对血管收缩剂的反应增强。尚不清楚肾循环中是否存在此类异常。本研究的目的是确定在8至10周的对照饮食（乙酰胆碱组，n = 6；血管紧张素II组，n = 6）或1%胆固醇饮食（乙酰胆碱组，n = 7；血管紧张素II组，n = 7）喂养后，麻醉兔对乙酰胆碱（ACh）或血管紧张素II（ANG II）输注的功能性肾反应。测量平均动脉压（MAP）、肾血流量（RBF）和肾小球滤过率（GFR）。肾血管阻力（RVR）计算为MAP/RBF。对于ANG II实验，输注卡托普利（15μg·kg⁻¹·min⁻¹）以抑制内源性ANG II的产生。在两个对照清除期后，将ACh（1μg·kg⁻¹·min⁻¹）或ANG II（0.5 ng·kg⁻¹·min⁻¹）注入肾动脉；在实验清除前使RBF稳定。ACh输注时RBF增加（对照：25±2至39±2 ml/min；胆固醇组：26±2至40±3 ml/min），ANG II输注时RBF降低（对照：40±4至25±3 ml/min；胆固醇组：36±3至24±2 ml/min）。硝酸盐/亚硝酸盐排泄也随ACh输注而增加（对照：2.3±1.0至5.2±1.8 nmol·kg⁻¹·min⁻¹；胆固醇组：2.3±0.3至6.0±1.3 nmol·kg⁻¹·min⁻¹）。然而，对照和胆固醇组在两种反应中均无显著差异。ACh和ANG II输注期间GFR未改变。两组对两种药物反应时的MAP、RVR以及尿钠和钾排泄无差异。这些结果表明，尽管存在显著的高胆固醇血症和大血管动脉粥样硬化，但肾循环中一氧化氮诱导的血管舒张和ANG II血管收缩的内皮依赖性调节均不受胆固醇喂养的影响。
