DeSouza Christopher A, Clevenger Christopher M, Greiner Jared J, Smith Derek T, Hoetzer Greta L, Shapiro Linda F, Stauffer Brian L
Integrative Vascular Biology Laboratory, Department of Kinesiology and Applied Physiology, University of Colorado, Boulder, CO 80309, USA.
J Physiol. 2002 Jul 1;542(Pt 1):255-62. doi: 10.1113/jphysiol.2002.019166.
Endothelium-dependent vasodilatation declines with advancing age in humans independently of disease. The mechanisms responsible for this decline are not clear. We determined whether the age-related reduction in endothelium-dependent vasodilatation in response to acetylcholine reflects a specific agonist-related defect or rather a more general endothelial cell vasomotor abnormality. Twenty-two young (23-35 years) and 41 older (50-76 years) healthy men were studied. Forearm blood flow (FBF) responses to intra-arterial infusions of acetylcholine, bradykinin, substance P, isoproterenol (isoprenaline) and sodium nitroprusside were measured by strain-gauge plethysmography. There were no differences in resting FBF between the young (3.9 +/- 0.2 ml (100 ml tissue)(-1) x min(-1)) and older men (4.0 +/- 0.2 ml (100 ml tissue)(-1) x min(-1)). The increase in FBF at the highest dose of acetylcholine was approximately 30 % lower (P < 0.01) in the older (from 4.0 +/- 0.2 to 12.3 +/- 0.7 ml (100 ml tissue)(-1) x min(-1)) compared with young men (from 3.9 +/- 0.2 to 17.1 +/- 1.5 ml (100 ml tissue)(-1) x min(-1)). In contrast to acetylcholine, the FBF responses to the other endothelial agonists were not impaired with age. The maximum increases in FBF in response to bradykinin (19.2 +/- 1.0 vs. 20.2 +/- 0.9 ml (100 ml tissue)(-1) x min(-1)), substance P (15.1 +/- 0.8 vs. 16.8 +/- 0.7 ml (100 ml tissue)(-1) x min(-1)) and isoproterenol (17.5 +/- 0.9 vs. 17.5 +/- 0.9 ml (100 ml tissue)(-1) x min(-1)) were not significantly different between the older and young subjects. There were no age-related differences in the FBF responses to sodium nitroprusside. These results demonstrate that, although acetylcholine-induced vasodilatation is impaired with age, forearm endothelial vasodilatation in response to bradykinin, substance P and isoproterenol are well preserved in healthy men. Moreover, these findings suggest that agonist-stimulated endothelium-dependent vasodilatation is not universally impaired with age.
在人类中，内皮依赖性血管舒张功能会随着年龄的增长而下降，且与疾病无关。导致这种下降的机制尚不清楚。我们确定了随着年龄增长，乙酰胆碱诱导的内皮依赖性血管舒张功能下降是反映了特定激动剂相关的缺陷，还是更普遍的内皮细胞血管舒缩异常。我们研究了22名年轻（23 - 35岁）和41名年长（50 - 76岁）的健康男性。通过应变片体积描记法测量前臂血流量（FBF）对动脉内输注乙酰胆碱、缓激肽、P物质、异丙肾上腺素和硝普钠的反应。年轻男性（3.9±0.2 ml（100 ml组织）⁻¹×min⁻¹）和年长男性（4.0±0.2 ml（100 ml组织）⁻¹×min⁻¹）的静息FBF没有差异。与年轻男性（从3.9±0.2增加到17.1±1.5 ml（100 ml组织）⁻¹×min⁻¹）相比，年长男性（从4.0±0.2增加到12.3±0.7 ml（100 ml组织）⁻¹×min⁻¹）在最高剂量乙酰胆碱作用下FBF的增加约低30%（P < 0.01）。与乙酰胆碱不同，年龄对其他内皮激动剂引起的FBF反应没有损害。年长和年轻受试者对缓激肽（19.2±1.0 vs. 20.2±0.9 ml（100 ml组织）⁻¹×min⁻¹）、P物质（15.1±0.8 vs. 16.8±0.7 ml（100 ml组织）⁻¹×min⁻¹）和异丙肾上腺素（17.5±0.9 vs. 17.5±0.9 ml（100 ml组织）⁻¹×min⁻¹）的FBF最大增加量没有显著差异。年龄对硝普钠引起的FBF反应没有差异。这些结果表明，虽然乙酰胆碱诱导的血管舒张功能随年龄受损，但健康男性前臂对缓激肽、P物质和异丙肾上腺素的内皮血管舒张功能保存良好。此外，这些发现表明激动剂刺激的内皮依赖性血管舒张功能并非普遍随年龄受损。
