INTRAVASCULAR PRESSURE AND ENDOTHELIAL FUNCTION IN HUMAN

人体血管内压力和内皮功能

• 批准号: 6418986
• 负责人: JULIO PANZA
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6418986
• 关键词: acetylcholine; artery; cardiovascular pharmacology; clinical research; human subject; hypertension; nitroferricyanide; vascular endothelium; vasodilation

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.

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结果尚不清楚。 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增加对人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名男性和4名女性;年龄：46+/-10岁）的臀脂肪活检中分离小动脉（内径：202+/-75微米）。 将动脉插管并在37 ℃充氧的腔室中灌注。 内皮依赖性和非依赖性的反应乙酰胆碱（乙酰胆碱;10-9至10-4 M）和硝普钠（SNP; 10 -9至10-4 M），分别获得孵育后的血管与递增的血管内压力为50，80，和120毫米汞柱各60分钟。 在50 mmHg下连续孵育3个时间后，在不同动脉中也获得了对Ach的反应。 直接从放大的数字图像测量动脉内径。 随着血管内压的升高，血管舒张反应显著降低（平均血管舒张：50、80和120 mmHg分别为62%、49%和26%; P<0.001）。 相比之下，对SNP的反应显示出随着压力增加血管舒张更大的非显著趋势（平均血管舒张：在50、80和120 mmHg下分别为40%、52%和57%; P=0.10）。 在相同血管内压下获得的Ach的连续剂量-反应曲线无差异（平均血管舒张：48%、46%和49%; P=0.61）。血管内压的瞬时升高显著抑制人阻力动脉的内皮依赖性血管舒张。 这些研究结果表明，血压升高本身可能会导致内皮功能障碍，在人类和高血压内皮功能障碍的病理生理学的影响。