Young D B, Lin H B, LeDuff J K
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505.
Am J Physiol. 1990 Apr;258(4 Pt 2):F1105-9. doi: 10.1152/ajprenal.1990.258.4.F1105.
The effects of short- and long-term administration of the calcium-entry blocker verapamil on regulation of renal hemodynamics and renin release were analyzed in anesthetized dogs at controlled levels of renal perfusion pressure between 110 and 60 mmHg. The following three groups of dogs were studied: a control group, an acutely treated verapamil group (initial dose of 150 micrograms/kg followed by 4 micrograms.kg-1.min-1), and a chronically treated verapamil group (240 mg per os twice each day). At 110 mmHg the renal blood flow (RBF) in the acutely and chronically treated groups was 53% greater than (P less than 0.03) and 79% greater than (P less than 0.01) that of the control group. Glomerular filtration rate (GFR) in the acutely and chronically treated groups was 64 and 92%, respectively, greater than (P less than 0.01 for both) that of the control group. Autoregulation of RBF and GFR was extremely effective in the control group, whereas it was severely impaired by acute and long-term treatment with verapamil. Renin release at 110 mmHg in the control and the acutely treated groups were similar, 3.36 +/- 0.96 and 4.46 +/- 0.64 U.min-1.g-1, respectively, although in the chronically treated group the rate of release was 8.89 +/- 2.60 U.min-1.g-1 (P less than 0.03). As perfusion pressure was reduced, the rate of release from the acutely treated group rose to higher levels than that of the control group; at 70 mmHg release from the acutely treated group was 88% greater than that of the control group (P less than 0.01). Verapamil profoundly alters regulation of renal hemodynamics and renin release and the effect is prominent during both short- and long-term administration.
在肾灌注压控制在110至60 mmHg的麻醉犬中，分析了钙通道阻滞剂维拉帕米短期和长期给药对肾血流动力学调节和肾素释放的影响。研究了以下三组犬：对照组、急性维拉帕米治疗组（初始剂量150微克/千克，随后4微克·千克-1·分钟-1）和慢性维拉帕米治疗组（每日口服240毫克，每日两次）。在110 mmHg时，急性和慢性治疗组的肾血流量（RBF）分别比对照组高53%（P<0.03）和79%（P<0.01）。急性和慢性治疗组的肾小球滤过率（GFR）分别比对照组高64%和92%（两者P<0.01）。对照组对RBF和GFR的自身调节非常有效，而急性和长期维拉帕米治疗严重损害了这种调节。对照组和急性治疗组在110 mmHg时的肾素释放相似，分别为3.36±0.96和4.46±0.64 U·分钟-1·克-1，尽管慢性治疗组的释放速率为8.89±2.60 U·分钟-1·克-1（P<0.03）。随着灌注压降低，急性治疗组的释放速率升至高于对照组的水平；在70 mmHg时，急性治疗组的释放比对照组高88%（P<0.01）。维拉帕米深刻改变肾血流动力学调节和肾素释放，且在短期和长期给药期间效果均显著。
