Taddei S, Virdis A, Mattei P, Ghiadoni L, Sudano I, Salvetti A
I Clinica Medica, University of Pisa, Italy.
Circulation. 1996 Sep 15;94(6):1298-303. doi: 10.1161/01.cir.94.6.1298.
Essential hypertension is characterized by impaired endothelium-dependent vasodilation. The present study was designed to investigate whether this abnormality is a primary defect or a consequence of blood pressure increases.
In offspring of essential hypertensive patients (n = 34) and normotensive subjects (n = 30), we evaluated forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms.100 mL-1.min-1), an endothelium-dependent vasodilator, and sodium nitroprusside (1, 2, and 4 micrograms.100 mL-1.min-1), an endothelium-independent vasodilator. Minimal forearm vascular resistances also were calculated as the ratio between mean intra-arterial pressure and maximal forearm blood flow induced by forearm ischemia and hand exercise. Vasodilation to acetylcholine was significantly (P < .01) blunted in offspring of hypertensive patients compared with offspring of normotensive subjects, whereas the responses to sodium nitroprusside and minimal forearm vascular resistances were similar. In two subgroups of 14 offspring of essential hypertensive patients but not in 10 offspring of normotensive subjects, vasodilation to acetylcholine was increased by intra-brachial L-arginine (1 mumol.100 mL-1.min-1), the substrate for nitric oxide synthesis, whereas in the other 10 and 8 offspring of essential hypertensive patients and normotensive subjects, respectively, cyclooxygenase blockade by intra-brachial indomethacin (50 micrograms.100 mL-1.min-1) was ineffective.
Offspring of essential hypertensive patients are characterized by a reduced response to acetylcholine linked to a defect in the nitric oxide pathway, suggesting that an impairment in nitric oxide production precedes the onset of 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。本研究旨在调查这种异常是原发性缺陷还是血压升高的结果。
在原发性高血压患者的后代（n = 34）和血压正常受试者的后代（n = 30）中，我们评估了由内皮依赖性血管舒张剂肱动脉内注射乙酰胆碱（0.15、0.45、1.5、4.5和15微克·100 mL-1·min-1）以及内皮非依赖性血管舒张剂硝普钠（1、2和4微克·100 mL-1·min-1）引起的前臂血流（应变片体积描记法）变化。最小前臂血管阻力也通过平均动脉内压与前臂缺血和手部运动诱导的最大前臂血流之间的比值来计算。与血压正常受试者的后代相比，高血压患者的后代对乙酰胆碱的血管舒张反应明显减弱（P <.01），而对硝普钠的反应和最小前臂血管阻力相似。在原发性高血压患者的14名后代的两个亚组中，但在血压正常受试者的10名后代中未观察到，一氧化氮合成底物肱动脉内注射L-精氨酸（1 μmol·100 mL-1·min-1）可增加对乙酰胆碱的血管舒张反应，而在原发性高血压患者和血压正常受试者的另外10名和8名后代中，肱动脉内注射吲哚美辛（50微克·100 mL-1·min-1）阻断环氧化酶则无效。
原发性高血压患者的后代对乙酰胆碱的反应降低，与一氧化氮途径缺陷有关，提示一氧化氮生成受损先于原发性高血压的发生。
