Divergent effects of ACE-inhibition and calcium channel blockade on NO-activity in systemic and renal circulation in essential hypertension

被引:12
作者
Dijkhorst-Oei, LT [1 ]
Beutler, JJ [1 ]
Stroes, ESG [1 ]
Koomans, HA [1 ]
Rabelink, TJ [1 ]
机构
[1] Univ Utrecht Hosp, Dept Nephrol & Hypertens, Utrecht, Netherlands
关键词
essential hypertension; nitric oxide; L-NMMA; angiotensin; converting enzyme inhibitor; calcium channel blocker; systemic vascular resistance; renal hemodynamics;
D O I
10.1016/S0008-6363(98)00124-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Nitric oxide is a vasodilating and blood pressure lowering substance. To investigate whether calcium antagonists or angiotensin-converting enzyme (ACE) inhibitors increase vascular nitric oxide activity, we assessed systemic and renal vascular sensitivity to nitric oxide synthase inhibition in hypertensives on and off medication. Methods: Ten essential hypertensive patients, aged 22-51 years, were studied 3 times: greater than or equal to 4 weeks off medication, after 3 weeks treatment with enalapril 20 mg twice a day and after 3 weeks nifedipine 60 mg/day. Each time, 24-h blood pressure registration was performed, followed by a clearance study to obtain a 3-h dose-response curve for intravenously infused NG-monomethyl-L-arginine (L-NMMA, respectively 0.75, 1.5 and 3.0 mg/kg/h). Results: L-NMMA. dose-dependently increased mean arterial pressure with 5+/-2 mmHg and systemic vascular resistance with 24+/-5% at maximum dose, whereas cardiac output decreased tall P<0.001). Enalapril and nifedipine treatment decreased blood pressure, while the L-NMMA-induced increase in systemic vascular resistance was potentiated (enalapril: 45+/-7% and nifedipine: 46+/-8%; both P<0.01). L-NMMA also dose-dependently decreased renal blood flow by 58+/-8% at maximum dose (P<0.001), but neither drug potentiated these effects. Conclusion: These results indicate that, in essential hypertensives, antihypertensive therapy with enalapril or nifedipine increases nitric oxide dependency of systemic vascular tone, which may play a role in the blood pressure lowering effect of these drugs. However, this phenomenon cannot be observed in the renal circulation, suggesting a different regulation of endothelium-dependent vasomotion in the hypertensive kidney. (C) 1998 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:402 / 409
页数:8
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