大鼠冠状动脉血管胆碱能反应而非α肾上腺素能反应的年龄相关性改变。

Age related alteration in cholinergic but not alpha adrenergic response of rat coronary vasculature.

作者信息

Su N, Narayanan N

机构信息

Department of Physiology, University of Western Ontario, London, Canada.

出版信息

Cardiovasc Res. 1993 Feb;27(2):284-90. doi: 10.1093/cvr/27.2.284.

DOI:10.1093/cvr/27.2.284

PMID:8097134

Abstract

OBJECTIVE

The aim was to determine whether aging alters coronary vascular responses to cholinergic and alpha adrenergic stimulation.

METHODS

Changes in coronary perfusion pressure and myocardial contractility in response to infusion of cholinergic and alpha adrenergic agonists and antagonists were determined in isolated Langendorff perfused hearts from adult (6-8 months old) and aged (28-30 months old) Fischer 344 rats.

RESULTS

In electrically paced hearts (250 beats.min-1), perfused at constant perfusate flow rate, the cholinergic agonist carbachol (10(-10)-10(6)M) elicited concentration dependent coronary vasoconstriction. The maximum response and the sensitivity to carbachol were more than twofold greater in the aged than in the adult heart: concentration of carbachol producing 50% increase in coronary perfusion pressure: adult 916(SEM 210) nM; aged 21(7) nM; p < 0.01. Under these experimental conditions, the negative inotropic response elicited by carbachol was also relatively greater (approximately twofold) in the aged hearts. A similar age related difference in coronary vascular response to carbachol was also observed in potassium (18 mM KCl) arrested, non-beating, constant flow perfused hearts. In adult and aged hearts, the carbachol induced vasoconstriction was mediated by vascular (M3) muscarinic receptors as judged from blockade of the response by the non-selective muscarinic receptor antagonist atropine, but not by the cardioselective (M2) muscarinic receptor antagonist AFDX-116. The Ca2+ channel antagonist verapamil markedly attenuated the carbachol induced coronary vasoconstriction, indicating that a large component of the contractile Ca2+ mobilised by vascular muscarinic receptor activation is derived via influx of extracellular Ca2+. The alpha adrenergic agonist phenylephrine (10(-10)-10(6)M) produced concentration dependent coronary vasoconstriction; there was no age related difference in this alpha adrenergic response.

CONCLUSIONS

There is striking enhancement of coronary vascular response to cholinergic but not alpha adrenergic stimuli with aging. Such age related cholinergic hypersensitivity may contribute to the high incidence of coronary artery spasm and impairment of coronary blood flow, cardiac energy metabolism, and contractile function that occurs with aging.

摘要

目的

确定衰老是否会改变冠状动脉对胆碱能和α肾上腺素能刺激的反应。

方法

在成年（6 - 8个月大）和老年（28 - 30个月大）的Fischer 344大鼠的离体Langendorff灌注心脏中，测定输注胆碱能和α肾上腺素能激动剂及拮抗剂后冠状动脉灌注压和心肌收缩性的变化。

结果

在以恒定灌注液流速灌注、电起搏（250次/分钟）的心脏中，胆碱能激动剂卡巴胆碱（10⁻¹⁰ - 10⁶M）引起浓度依赖性冠状动脉收缩。老年心脏中对卡巴胆碱的最大反应和敏感性比成年心脏高出两倍多：使冠状动脉灌注压升高50%的卡巴胆碱浓度：成年为916（标准误210）nM；老年为21（7）nM；p < 0.01。在这些实验条件下，卡巴胆碱引起的负性变力反应在老年心脏中也相对更大（约两倍）。在钾（18 mM KCl）停搏、无搏动、恒流灌注的心脏中，也观察到了类似的与年龄相关的冠状动脉对卡巴胆碱反应的差异。在成年和老年心脏中，从非选择性毒蕈碱受体拮抗剂阿托品对反应的阻断判断，卡巴胆碱诱导的血管收缩是由血管（M3）毒蕈碱受体介导的，而不是由心脏选择性（M2）毒蕈碱受体拮抗剂AFDX - 116介导的。钙通道拮抗剂维拉帕米显著减弱了卡巴胆碱诱导的冠状动脉收缩，表明血管毒蕈碱受体激活所动员的收缩性钙的很大一部分是通过细胞外钙内流获得的。α肾上腺素能激动剂去氧肾上腺素（10⁻¹⁰ - 10⁶M）产生浓度依赖性冠状动脉收缩；在这种α肾上腺素能反应中没有与年龄相关的差异。