Taddei S, Virdis A, Ghiadoni L, Uleri S, Magagna A, Salvetti A
I Clinica Medica, University of Pisa, Italy.
Hypertension. 1997 Dec;30(6):1606-12. doi: 10.1161/01.hyp.30.6.1606.
Essential hypertension is characterized by impaired endothelium-dependent vasodilation. The present study was designed to test whether antihypertensive treatment with the calcium antagonist lacidipine can improve endothelium-dependent vasodilation in essential hypertensive patients. In 12 normotensive subjects (mean age, 47.8+/-8.6 years; blood pressure, 118.6+/-4.2/76.7+/-3.9 mm Hg) and 19 hypertensive patients (mean age, 49.4+/-10.2 years; blood pressure; 153.5+/-13.3/101.3+/-6.4 mm Hg), we studied forearm blood flow modifications (strain-gauge plethysmography) induced by intrabrachial infusion of acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute) and bradykinin (5, 15, and 50 ng/100 mL per minute), two endothelium-dependent vasodilators that act through different receptors and signal transduction pathways, and sodium nitroprusside (1, 2, and 4 microg/100 mL per minute), an endothelium-independent vasodilator. In essential hypertensive patients, vascular reactivity was repeated during prolonged (8 weeks of oral treatment at 6 mg/d) lacidipine administration and 2 weeks after withdrawal of chronic (32-week) treatment. Hypertensive patients showed significantly (P<.01) blunted vasodilation in response to acetylcholine (vascular resistance, 31.5+/-4.9 to 7.6+/-2.4 SU) and bradykinin (vascular resistance, 32.3+/-5.8 to 8.5+/-3.0 SU) compared with control subjects (vascular resistance: acetylcholine, 24.3+/-3.9 to 3.7+/-1.2 SU; bradykinin, 24.7+/-0.4 to 4.1+/-1.3 SU), whereas the response to sodium nitroprusside was similar. After either 8 or 32 weeks of lacidipine treatment, the vasodilation in response to acetylcholine (30.6+/-7.7 to 5.7+/-1.5 and 34.3+/-6.6 to 5.9+/-1.9 SU, respectively) and bradykinin (31.3+/-7.2 to 6.4+/-1.6 and 33.7+/-5.4 to 6.1+/-1.5 SU, respectively), but not to sodium nitroprusside, proved to be significantly (P<.05) increased compared with baseline. In essential hypertensive patients, oral treatment with lacidipine increased forearm vasodilation in response to acetylcholine and bradykinin, suggesting that this drug can improve endothelial function in patients with essential hypertension.
原发性高血压的特征是内皮依赖性血管舒张功能受损。本研究旨在测试钙拮抗剂拉西地平的降压治疗是否能改善原发性高血压患者的内皮依赖性血管舒张功能。在12名血压正常的受试者(平均年龄47.8±8.6岁;血压118.6±4.2/76.7±3.9 mmHg)和19名高血压患者(平均年龄49.4±10.2岁;血压153.5±13.3/101.3±6.4 mmHg)中,我们研究了通过肱动脉内输注乙酰胆碱(0.15、0.45、1.5、4.5和15 μg/100 mL每分钟)、缓激肽(5、15和50 ng/100 mL每分钟)和硝普钠(1、2和4 μg/100 mL每分钟)引起的前臂血流变化(应变片体积描记法)。乙酰胆碱和缓激肽是两种通过不同受体和信号转导途径起作用的内皮依赖性血管舒张剂,硝普钠是一种不依赖内皮的血管舒张剂。在原发性高血压患者中,在长期(6 mg/d口服治疗8周)服用拉西地平期间和慢性(32周)治疗停药2周后重复进行血管反应性测试。与对照组相比,高血压患者对乙酰胆碱(血管阻力从31.5±4.9至7.6±2.4 SU)和缓激肽(血管阻力从32.3±5.8至8.5±3.0 SU)的血管舒张反应明显减弱(P<0.01)(血管阻力:乙酰胆碱,24.3±3.9至3.7±1.2 SU;缓激肽,24.7±0.4至4.1±1.3 SU),而对硝普钠的反应相似。在拉西地平治疗8周或32周后,对乙酰胆碱(分别为30.6±7.7至5.7±1.5和34.3±6.6至5.9±1.9 SU)和缓激肽(分别为31.3±7.2至6.4±1.6和33.7±5.4至6.1±1.5 SU)的血管舒张反应,但对硝普钠的反应未增加),与基线相比有显著(P<0.05)增加。在原发性高血压患者中,口服拉西地平可增加前臂对乙酰胆碱和缓激肽的血管舒张反应,表明该药物可改善原发性高血压患者的内皮功能。