Cardillo C, Kilcoyne C M, Quyyumi A A, Cannon R O, Panza J A
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1650, USA.
Circulation. 1998 Mar 10;97(9):851-6. doi: 10.1161/01.cir.97.9.851.
Patients with essential hypertension have impaired endothelial NO activity, but the mechanism underlying this abnormality is unknown.
To investigate whether the endothelial dysfunction of hypertensive patients is related to a selective defect in NO synthesis, we studied the forearm blood flow responses to intra-arterial infusion of acetylcholine (7.5 to 30 microg/min), an endothelial agonist linked to NO synthase through the Ca2+ signaling pathway, and isoproterenol (50 to 200 ng/min), a beta-adrenoceptor agonist that stimulates NO production by increasing intracellular cAMP, in 12 normotensive subjects and 12 hypertensive patients. The infusion of isoproterenol was repeated during the concurrent blockade of NO synthesis by NG-monomethyl-L-arginine (L-NMMA; 4 micromol/min). The vasodilator response to acetylcholine was significantly reduced in hypertensives compared with normotensives (maximum blood flow: 10.4+/-4.6 versus 14.4+/-3.7 mL x min[-1] x dL[-1]; P=.008). However, the vasodilator effect of isoproterenol was similar in normotensives and hypertensives (maximum blood flow: 14.4+/-5.4 versus 13.5+/-5 mL x min[-1] x dL[-1]; P=.56) and was significantly (both P<.01) and equally blunted by L-NMMA in both groups (maximum blood flow: 11+/-3 mL x min[-1] x dL[-1] in normotensives versus 10.8+/-3.9 mL x min[-1] x dL[-1] in hypertensives; P=.77). The vasodilator response to sodium nitroprusside (0.8 to 3.2 microg/min), an exogenous NO donor, was similar in both groups and was not modified by L-NMMA.
Hypertensive patients have impaired endothelium-dependent vasodilation in response to acetylcholine but preserved NO activity in response to beta-adrenergic stimulation. These findings suggest that the endothelial dysfunction in essential hypertension is due to a selective abnormality of NO synthesis, probably related to a defect in the phosphatidylinositol/Ca2+ signaling pathway.
原发性高血压患者存在内皮一氧化氮（NO）活性受损的情况，但这种异常的潜在机制尚不清楚。
为了研究高血压患者的内皮功能障碍是否与NO合成的选择性缺陷有关，我们在12名血压正常的受试者和12名高血压患者中，研究了前臂血流对动脉内注射乙酰胆碱（7.5至30微克/分钟）和异丙肾上腺素（50至200纳克/分钟）的反应。乙酰胆碱是一种通过Ca2+信号通路与一氧化氮合酶相关的内皮激动剂，而异丙肾上腺素是一种β-肾上腺素能激动剂，通过增加细胞内cAMP来刺激NO生成。在通过NG-单甲基-L-精氨酸（L-NMMA；4微摩尔/分钟）同时阻断NO合成的过程中，重复注射异丙肾上腺素。与血压正常者相比，高血压患者对乙酰胆碱的血管舒张反应显著降低（最大血流量：10.4±4.6与14.4±3.7毫升·分钟-1·分升-1；P = 0.008）。然而，异丙肾上腺素在血压正常者和高血压患者中的血管舒张作用相似（最大血流量：14.4±5.4与13.5±5毫升·分钟-1·分升-1；P = 0.56），并且在两组中均被L-NMMA显著（P均<0.01）且同等程度地减弱（血压正常者最大血流量：11±3毫升·分钟-1·分升-1，高血压患者为10.8±3.9毫升·分钟-1·分升-1；P = 0.77）。两组对外源性NO供体硝普钠（0.8至3.2微克/分钟）的血管舒张反应相似，且不受L-NMMA影响。
高血压患者对乙酰胆碱的内皮依赖性血管舒张功能受损，但对β-肾上腺素能刺激的NO活性保留。这些发现表明，原发性高血压中的内皮功能障碍是由于NO合成的选择性异常，可能与磷脂酰肌醇/Ca2+信号通路的缺陷有关。
