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人骨骼肌营养动脉中的α1-肾上腺素能反应性:降低细胞外 pH 值的影响。

α1-Adrenergic responsiveness in human skeletal muscle feed arteries: the impact of reducing extracellular pH.

机构信息

Geriatric Research, Education and Clinical Center, George E. Whalen VA Medical Center, Salt Lake City, UT, USA.

出版信息

Exp Physiol. 2013 Jan;98(1):256-67. doi: 10.1113/expphysiol.2012.066613. Epub 2012 Jul 13.

DOI:10.1113/expphysiol.2012.066613
PMID:22798402
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4465408/
Abstract

Graded exercise results not only in the modulation of adrenergic mediated smooth muscle tone and a preferential increase in blood flow to the active skeletal muscle termed 'functional sympatholysis', but is also paralleled by metabolically induced reductions in pH. We therefore sought to determine whether pH attenuates α(1)-adrenergic receptor sensitivity in human feed arteries. Feed arteries (560 ± 31 μm i.d.) were harvested from 24 humans (55 ± 4 years old) and studied using the isometric tension technique. Vessel function was assessed using KCl, phenylephrine (PE), ACh and sodium nitroprusside (SNP) concentration-response curves to characterize non-receptor-mediated and receptor-mediated vasocontraction, as well as endothelium-dependent and -independent vasorelaxation, respectively. All concentration-response curves were obtained from (originally contiguous) vessel rings in separate baths with a pH of 7.4, 7.1, 6.8 or 6.5. Reduction of the pH, via HCl, reduced maximal PE-induced vasocontraction (pH 7.4 = 85 ± 19, pH 7.1 = 57 ± 16, pH 6.8 = 34 ± 15 and pH 6.5 = 16 ± 5% KCl(max)), which was partly due to reduced smooth muscle function, as assessed by KCl (pH 7.4 = 88 ± 13, pH 7.1 = 67 ± 8, pH 6.8 = 67 ± 9 and pH 6.5 = 58 ± 8% KCl(max)). Graded acidosis had no effect on maximal vasorelaxation. In summary, these data reveal that reductions in extracellular pH attenuate α(1)-mediated vasocontraction, which is partly explained by reduced smooth muscle function, although vasorelaxation in response to ACh and SNP remained intact. These findings support the concept that local acidosis is likely to contribute to functional sympatholysis and exercise hyperaemia by opposing sympathetically mediated vasoconstriction while not impacting vasodilatation.

摘要

运动训练不仅会导致肾上腺素能介导的平滑肌张力调节,并且会优先增加被称为“功能性解交感神经作用”的活跃骨骼肌的血流量,同时还伴随着代谢诱导的 pH 值降低。因此,我们试图确定 pH 值是否会降低人肠系膜动脉中的 α(1)-肾上腺素能受体敏感性。从 24 名成年人(55 ± 4 岁)中采集肠系膜动脉(内径 560 ± 31 μm),并使用等长张力技术进行研究。使用 KCl、苯肾上腺素 (PE)、乙酰胆碱 (ACh) 和硝普钠 (SNP) 浓度-反应曲线评估血管功能,以分别表征非受体介导和受体介导的血管收缩,以及内皮依赖性和非依赖性血管舒张。所有浓度-反应曲线均从 pH 值分别为 7.4、7.1、6.8 或 6.5 的单独浴中(原始连续)的血管环获得。通过 HCl 降低 pH 值会降低最大 PE 诱导的血管收缩(pH 7.4 = 85 ± 19,pH 7.1 = 57 ± 16,pH 6.8 = 34 ± 15,pH 6.5 = 16 ± 5% KCl(max)),这部分是由于平滑肌功能降低所致,如 KCl 评估所示(pH 7.4 = 88 ± 13,pH 7.1 = 67 ± 8,pH 6.8 = 67 ± 9,pH 6.5 = 58 ± 8% KCl(max))。分级酸中毒对最大血管舒张没有影响。总之,这些数据表明,细胞外 pH 值降低会减弱 α(1)-介导的血管收缩,这部分是由于平滑肌功能降低所致,尽管对 ACh 和 SNP 的血管舒张反应仍然完整。这些发现支持这样的概念,即局部酸中毒可能通过拮抗交感神经介导的血管收缩来促进功能性解交感神经作用和运动性充血,而不会影响血管舒张。

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