Dijkhorst-Oei L T, Beutler J J, Stroes E S, Koomans H A, Rabelink T J
Department of Nephrology and Hypertension, University Hospital, Utrecht, The Netherlands.
Cardiovasc Res. 1998 Nov;40(2):402-9. doi: 10.1016/s0008-6363(98)00124-2.
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.
Ten essential hypertensive patients, aged 22-51 years, were studied 3 times: > or = 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).
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 (all 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.
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.
一氧化氮是一种血管舒张和降血压物质。为研究钙拮抗剂或血管紧张素转换酶（ACE）抑制剂是否会增加血管一氧化氮活性，我们评估了正在服药和未服药的高血压患者对一氧化氮合酶抑制的全身和肾血管敏感性。
对10名年龄在22 - 51岁的原发性高血压患者进行了3次研究：停药≥4周后、每天两次服用20 mg依那普利治疗3周后以及每天服用60 mg硝苯地平治疗3周后。每次均进行24小时血压记录，随后进行清除率研究，以获得静脉输注NG-单甲基-L-精氨酸（L-NMMA，分别为0.75、1.5和3.0 mg/kg/h）的3小时剂量反应曲线。
L-NMMA剂量依赖性地使平均动脉压在最大剂量时升高5±2 mmHg，全身血管阻力升高24±5%，而心输出量下降（所有P<0.001）。依那普利和硝苯地平治疗可降低血压，同时L-NMMA诱导的全身血管阻力增加得到增强（依那普利：45±7%，硝苯地平：46±8%；均P<0.01）。L-NMMA在最大剂量时也剂量依赖性地使肾血流量减少58±8%（P<0.001），但两种药物均未增强这些作用。
这些结果表明，在原发性高血压患者中，依那普利或硝苯地平的抗高血压治疗增加了全身血管张力对一氧化氮的依赖性，这可能在这些药物的降血压作用中发挥作用。然而，在肾循环中未观察到这种现象，提示高血压肾脏中内皮依赖性血管运动的调节不同。
