Rossi G P, Taddei S, Virdis A, Ghiadoni L, Albertin G, Favilla S, Sudano I, Pessina A C, Salvetti A
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Hypertension. 2001 Feb;37(2):293-300. doi: 10.1161/01.hyp.37.2.293.
A deletion/insertion (D/I) polymorphism within the ACE gene may increase the risk of cardiovascular events through still unknown mechanisms. The latter may involve increased angiotensin II-induced NO breakdown and/or reduced agonist-mediated NO release. We therefore investigated whether the D allele of the ACE gene affects endothelium-dependent vasodilatation in mild-to-moderate primary hypertensive patients and healthy normotensive subjects. We compared in a cross-sectional study the forearm blood flow response of the 3 D/I genotypes with 5 incrementally increasing doses of the endothelium-dependent vasodilator acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg. 100 mL(-1). min(-1)) in 142 subjects: 103 mild-to-moderate uncomplicated primary hypertensives (49.3+/-9.1 years old, 152+/-11/99+/-5 mm Hg) and 39 normotensives (44.6+/-15.3 years old, 122+/-12/78+/-6 mm Hg). We also assessed the endothelium-independent vasodilatation in the forearm, as blood flow response to 3 incrementally increasing doses of sodium nitroprusside (1, 2, and 4 microg. 100 mL(-1). min(-1)). The overall genotype distribution was II, n=10; ID, n=70; and DD, n=62. It did not differ significantly between primary hypertensives and normotensives. A significant blunting of endothelium-dependent vasodilatation in primary hypertensive patients compared with normotensive subjects (P:<0.001) was found. No effect of the DI genotype on endothelium-dependent and -independent vasodilatation was detected. Thus, these results obtained in a relatively large population do not support the contention that the D allele is associated with a blunting of either stimulated endothelial NO or donated NO responses in both mild-to-moderate primary hypertensive patients and normotensive subjects.
血管紧张素转换酶（ACE）基因中的缺失/插入（D/I）多态性可能通过尚不明确的机制增加心血管事件的风险。这些机制可能涉及血管紧张素II诱导的一氧化氮（NO）分解增加和/或激动剂介导的NO释放减少。因此，我们研究了ACE基因的D等位基因是否会影响轻至中度原发性高血压患者和健康血压正常受试者的内皮依赖性血管舒张功能。在一项横断面研究中，我们比较了142名受试者（103名轻至中度未并发原发性高血压患者，年龄49.3±9.1岁，收缩压/舒张压为152±11/99±5 mmHg；39名血压正常者，年龄44.6±15.3岁，收缩压/舒张压为122±12/78±6 mmHg）中3种D/I基因型对5种递增剂量的内皮依赖性血管舒张剂乙酰胆碱（0.15、0.45、1.5、4.5和15 μg·100 mL⁻¹·min⁻¹）的前臂血流反应。我们还评估了前臂对3种递增剂量硝普钠（1、2和4 μg·100 mL⁻¹·min⁻¹）的血流反应，以此作为非内皮依赖性血管舒张功能的评估指标。总体基因型分布为：II型，n = 10；ID型，n = 70；DD型，n = 62。原发性高血压患者和血压正常者之间的基因型分布无显著差异。与血压正常者相比，原发性高血压患者的内皮依赖性血管舒张功能明显减弱（P < 0.001）。未检测到D/I基因型对内皮依赖性和非内皮依赖性血管舒张功能有影响。因此，在相对较大人群中获得的这些结果不支持以下观点：在轻至中度原发性高血压患者和血压正常者中，D等位基因与刺激内皮源性NO或外源性NO反应减弱有关。
