衰老豚鼠离体心肌细胞对异丙肾上腺素的收缩反应降低。

Decreased contractile responses to isoproterenol in isolated cardiac myocytes from aging guinea-pigs.

作者信息

Ferrara N, O'Gara P, Wynne D G, Brown L A, del Monte F, Poole-Wilson P A, Harding S E

机构信息

Department of Cardiac Medicine, National Heart and Lung Institute, London, UK.

出版信息

J Mol Cell Cardiol. 1995 May;27(5):1141-50. doi: 10.1016/0022-2828(95)90050-0.

DOI:10.1016/0022-2828(95)90050-0

PMID:7473772

Abstract

We have characterized the age-related changes of contractility and beta-adrenoceptor function in isolated cardiac myocytes from guinea-pigs. We used either adult animals from 2 to 14 weeks of age, where body weight increases linearly with age, or senescent ones aged between 53-65 weeks. There was some indication of a decrease in contractility in maximum Ca2+ with age, with significant differences between a young (< or = 4 weeks, weight < 400 g) and aged (> or = 8 weeks, weight > 600 g) group in contraction amplitude expressed as percentage shortening (but not when expressed as micron change in length) or contraction and relaxation velocities. This decline was continued into senescence, and ANOVA showed a significant difference between the three groups for contraction amplitude (percentage shortening, 12.2 +/- 0.9%, young, n = 31; 9.5 +/- 0.6%, n = 28 aged; 6.7 +/- 0.8%, n = 6, senescent; P = 0.005), and contraction or relaxation velocities (P < 0.001). There was a more pronounced decline in maximum response to isoproterenol with age. ANOVA for the maximum isoproterenol response for the three divisions showed significant differences for percentage shortening (11.8 +/- 0.7%, n = 30, young; 7.9 +/- 0.5%, n-28, aged and 5.5 +/- 1.1%, n = 6, senescent; P < 0.001), velocities of contraction (P < 0.001) and relaxation (P < 0.001), and normalized velocities of contraction (P < 0.001) and relaxation (P < 0.01) at maximum isoproterenol, as well as in ISO EC50 (P < 0.001) and isoproterenol/Ca2+ ratio (P < 0.02). A general decrease in contractility of the myocyte occurs as the animal ages, with maximum contraction amplitude being reduced and velocity of contraction and relaxation slowed. The effect was more pronounced for beta-adrenoceptor stimulation than for high Ca2+, suggesting a specific lesion in the adenylate cyclase related pathway. Much of the change occurred between the young adult (< or = 4 weeks) and the aged adult (> or = 8 weeks), although the trend was continued in senescent animals (> 52 weeks).

摘要

我们已经描述了豚鼠离体心肌细胞收缩性和β - 肾上腺素能受体功能随年龄的变化。我们使用了2至14周龄的成年动物，其体重随年龄呈线性增加，以及53 - 65周龄的衰老动物。有迹象表明，随着年龄增长，最大Ca2 + 时的收缩性有所下降，在以缩短百分比表示收缩幅度时（但以长度微米变化表示时则不然），年轻组（≤4周，体重<400 g）和老年组（≥8周，体重>600 g）之间存在显著差异，收缩和舒张速度也有差异。这种下降在衰老过程中持续存在，方差分析显示三组之间收缩幅度（缩短百分比，年轻组12.2±0.9%，n = 31；老年组9.5±0.6%，n = 28；衰老组6.7±0.8%，n = 6；P = 0.005）、收缩或舒张速度（P < 0.001）存在显著差异。随着年龄增长，对异丙肾上腺素的最大反应下降更为明显。对三组的异丙肾上腺素最大反应进行方差分析显示，在最大异丙肾上腺素作用下，缩短百分比（年轻组11.8±0.7%，n = 30；老年组7.9±0.5%，n = 28；衰老组5.5±1.1%，n = 6；P < 0.001）、收缩速度（P < 0.001）和舒张速度（P < 0.001）、收缩和舒张的标准化速度（P < 0.001）以及舒张（P < 0.01），以及异丙肾上腺素EC50（P < 0.001）和异丙肾上腺素/Ca2 + 比值（P < 0.02）均存在显著差异。随着动物年龄增长，心肌细胞收缩性普遍下降，最大收缩幅度减小，收缩和舒张速度减慢。β - 肾上腺素能刺激的影响比高Ca2 + 更明显，提示腺苷酸环化酶相关途径存在特定损伤。大部分变化发生在年轻成年期（≤4周）和老年成年期（≥8周）之间，尽管衰老动物（>52周）也持续存在这种趋势。