INTRAVASCULAR PRESSURE AND ENDOTHELIAL FUNCTION IN HUMAN

高血压与内皮依赖性血管扩张功能降低有关。然而，内皮功能障碍是否是血压升高的原因或后果尚不清楚。因此，为了确定高血压是否可以直接导致内皮功能障碍，我们研究了动脉内压增加对人类微血管内皮依赖性血管扩张的影响。从12例健康正常血压受试者的臀部脂肪活检中分离出小动脉(内径：202±75微米)(男8例，女4例；年龄46±10岁)。动脉在37℃氧气室中插管和灌流，分别对乙酰胆碱(Ach；10-9~10-4M)和硝普钠(SNP；10-9~10-4M)有内皮依赖性和非内皮依赖性反应。在50毫米汞柱下连续3个潜伏期后，不同的动脉对Ach也有反应。根据放大的数字图像直接测量动脉内径。随着血管内压的升高，血管扩张剂对乙酰胆碱的反应显著降低(50、80和120毫米汞柱时的平均血管扩张分别为62%、49%和26%；P&lt；0.001)。相反，SNP的反应没有显示出随着压力的增加而更大的血管扩张的显著趋势(50、80和120毫米汞柱时的平均血管扩张分别为40%、52%和57%；P=0.10)。在相同的血管内压下，Ach的连续剂量-反应曲线没有差异(平均血管扩张：48%、46%和49%；P=0.61)。短暂的血管内压升高显著抑制人体阻力动脉的内皮依赖性血管扩张。这些发现表明，血压升高本身可能导致人类的内皮功能障碍，并对高血压患者内皮功能障碍的病理生理学有一定的影响。

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.