INTRAVASCULAR PRESSURE AND ENDOTHELIAL FUNCTION IN HUMAN

高血压与内皮依赖性血管舒张功能降低有关。然而，内皮功能障碍是血压升高的原因还是后果尚不清楚。因此，为了确定高血压是否可以直接诱导内皮功能障碍，我们研究了动脉内压升高对人体微血管内皮依赖性血管舒张的影响。从12名健康血压正常受试者（8男4女，年龄46+/-10岁）的臀脂肪活检中分离出小动脉（内径：202+/-75微米）。在37℃充氧的腔室中插管和灌注动脉，分别在血管内压力分别增加50、80和120 mmHg 60分钟后，获得乙酰胆碱（Ach；10-9至10-4 M）和硝普钠（SNP； 10-9至10-4 M）的内皮依赖性和非依赖性反应。在50 mmHg连续3个潜伏期后，不同动脉对乙酰胆碱的反应也得到了。动脉内径直接由放大的数字图像测量。随着血管内压力的增加，血管舒张剂对乙酰胆碱的反应显著降低（在50、80和120 mmHg时，平均血管舒张度分别为62%、49%和26%；P<0.001）。相反，对SNP的反应显示，随着压力的增加，血管舒张的趋势不明显（在50、80和120 mmHg时，平均血管舒张度分别为40%、52%和57%；P=0.10）。在相同血管内压力下获得的乙酰胆碱的连续剂量反应曲线没有差异（平均血管舒张度：48%，46%和49%；P=0.61）。血管内压力的短暂升高可显著抑制人阻力动脉内皮依赖性血管舒张。这些发现表明，血压升高本身可能导致人类内皮功能障碍，并对高血压患者内皮功能障碍的病理生理学有影响。

Hypertension is associated with decreased endothelium-dependent vasodilation. However, whether endothelial dysfunction is a cause or a consequence of elevated blood pressure is unknown. Therefore, to determine whether hypertension can directly induce endothelial dysfunction, we investigated the effect of increases in intra-arterial pressure on endothelium-dependent vasodilation of the human microvasculature. Small arteries (internal diameter: 202+/-75 microns) were isolated from gluteal fat biopsies in 12 healthy normotensive subjects (8 men and 4 women; age: 46+/-10 years). Arteries were cannulated and perfused in chambers oxygenated at 37 C. Endothelium-dependent and -independent responses to acetylcholine (Ach;10-9 to 10-4 M) and sodium nitroprusside (SNP; 10-9 to 10-4 M), respectively, were obtained after incubating the vessel with incremental intra-vascular pressures of 50, 80, and 120 mmHg for 60 min each. The response to Ach was also obtained in different arteries after 3 consecutive incubation periods at 50 mmHg. Arterial internal diameter was measured directly from amplified digital images. A significant reduction in the vasodilator response to Ach was observed with increases in intra-vascular pressure (mean vasodilation: 62%, 49%, and 26% at 50, 80, and 120 mmHg, respectively; P<0.001). In contrast, the response to SNP showed a non-significant trend toward greater vasodilation with increases in pressure (mean vasodilation: 40%, 52%, and 57% at 50, 80, and 120 mmHg, respectively; P=0.10). There was no difference in the consecutive dose-response curves to Ach obtained at the same intra-vascular pressure (mean vasodilation: 48%, 46%, and 49%; P=0.61). Transient increases in intra-vascular pressure significantly depress endothelium-dependent vasodilation in human resistance arteries. These findings suggest that elevated blood pressure per se may cause endothelial dysfunction in humans and have implications for the pathophysiology of endothelial dysfunction in hypertension.