INCREASED ENDOTHELIN VASOCONSTRICTOR ACTIVITY IN ESSENTIAL HYPERTENSION

高血压患者（HT）的一氧化氮水平受损， 氧化物（NO）活性，但这种异常的机制 不明我们最近观察到内皮素增加 (ET)血管收缩张力在HTs相关的生产增加 肽。在本研究中，我们调查了 HT的ET活性增加可能有助于其受损 NO依赖性血管舒张功能。为此，血管扩张剂 对乙酰胆碱（ACh; 7.5、15和30 ug/min）的反应， 内皮依赖性血管扩张剂和硝普钠 (SNP 0.8、1.6和3.2 μ g/min），外源性NO供体， 在非选择性阻断ETA和ETB之前和之后评估 受体的联合输注BQ-123（ETA阻滞剂; 100 BQ-788（ETB阻断剂; 50 nmol/min持续60 min） HT将药物注入肱动脉和前臂血液 通过应变计体积描记术测量流量（FBF）。的 3种剂量ACh诱导的FBF较基线增加， 通过ET受体的非选择性阻断显著增强 (0.47+/-0.21（平均值+/-SEM）、2.73+/-2.08和4.71+/-2.48 mL/min/dL，之前为3.38+/-1.41，6.06 +/-2.56，8.67+/-3.06 ET拮抗作用后的血流量（mL/min/dL; P=0.01）。相反，ET受体 阻断并没有显著改变血管对 3剂SNP（2.85 ± 0.95、4.76 ± 1.47和7.18 ± 2.27 mL/min/dL，之前为3.28+/-1.01，4.94 +/-1.48和6.5+/-1.84 mL/min/dL（P=0.97）。这些发现表明 HT患者的内皮血管舒张功能在 阻断ET受体，表明ET活性增加 可能参与其内皮细胞的病理生理学 功能障碍

Hypertensive patients (HTs) have impaired nitric oxide (NO) activity, but the mechanism underlying this abnormality is unknown. We have recently observed an increased endothelin (ET) vasoconstrictor tone in HTs related to increased production of the peptide. In the present study, we investigated whether the increased ET activity of HTs could contribute to their impaired NO-dependent vasodilator function. To this end, the vasodilator responses to acetylcholine (ACh; 7.5, 15, and 30 ug/min), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP; 0.8,1.6, and 3.2 ug/min), an exogenous NO donor, were assessed before and after nonselective blockade of ETA and ETB receptors by combined infusion of BQ-123 (ETA blocker; 100 nmol/min) and BQ-788 (ETB blocker; 50 nmol/min for 60 min) in 6 HTs. Drugs were infused into the brachial artery and forearm blood flow (FBF) was measured by strain-gauge plethysmography. The increases in FBF from baseline induced by the 3 doses of ACh were significantly potentiated by nonselective blockade of ET receptors (0.47+/-0.21(mean+/-SEM), 2.73+/-2.08, and 4.71+/-2.48 mL/min/dL before vs 3.38+/-1.41, 6.06+/-2.56, and 8.67+/-3.06 mL/min/dL after ET antagonism; P=0.01). In contrast, ET receptor blockade did not significantly modify vascular responsiveness to the 3 doses of SNP (2.85+/-0.95, 4.76+/-1.47, and 7.18+/-2.27 mL/min/dL before vs 3.28+/-1.01, 4.94+/-1.48, and 6.5+/-1.84 mL/min/dL after ET antagonism (P=0.97). These findings indicate that endothelial vasodilator function in HTs improves after blockade of ET receptors, suggesting that an increased ET activity may be involved in the pathophysiology of their endothelial dysfunction.