AGING ALTERS THE FORCE-FREQUENCY RELATIONSHIP AND TOXICITY OF OXIDATIVE STRESS IN RABBIT HEART
AGING ALTERS THE FORCE-FREQUENCY RELATIONSHIP AND TOXICITY OF OXIDATIVE STRESS IN RABBIT HEART
复制标题
DOI：
10.1016/0024-3205(91)90215-w
复制
发表时间：
1991-01-01
期刊：
影响因子：
6.1
通讯作者：
OLSON, RD
中科院分区：
文献类型：
--
作者：
CUSACK, BJ;MUSHLIN, PS;OLSON, RD
在已知增加细胞质钙（收缩和氧化应激频率增加）的条件下研究成年（6个月）和衰老（> 5岁）兔心房。 在收缩频率为1/sec时，衰老和成人心房的心脏舒张（90%舒张时间）相似，但在收缩频率为2或3/sec时，衰老心房的舒张明显较慢（P < 0.05）。 另外的实验表明，H2 O2（500 μ M），一种强氧化剂，在衰老的心房中增加静息力和降低发展力（DF）的速度比成年心房快得多;然而，DF的最大降低在衰老的制备中较少（成年= 81 +/- 6%，衰老= 42 +/- 27%的pre-H2 O2值; P < 0.05）。 H2 O2的作用与衰老相关的差异并不仅仅是由于衰老心脏通过谷胱甘肽途径解毒氧化应激的能力降低。 这两个基础谷胱甘肽（GSH）的浓度和H2 O2介导的GSH的减少是相似的成人和衰老的心室准备，谷胱甘肽过氧化物酶和谷胱甘肽还原酶的活动。 这些观察结果表明，已知的增加细胞质钙的干预措施可以通过可能独立于谷胱甘肽途径的机制放大与年龄相关的心脏松弛损伤。
Adult (6 months) and senescent (> 5 years) rabbit atria were studied under conditions known to increase cytoplasmic calcium (increased frequency of contraction and oxidative stress). At a contraction frequency of 1/sec, cardiac relaxation (90% relaxation time) was similar in senescent and adult atria but at a frequency of 2 or 3/sec, relaxation was significantly slower in senescent preparations (P < 0.05). Additional experiments indicated that H2O2 (500-mu-M), a powerful oxidant, increased resting force and decreased developed force (DF) much more rapidly in senescent than adult atria; the maximum decrease in DF, however, was less in senescent preparations (adult = 81 +/- 6% and senescent = 42 +/- 27% of pre-H2O2 values; P < 0.05). Age-related differences in effects of H2O2 did not result simply from a decreased ability of senescent hearts to detoxify an oxidative stress by the glutathione pathway. Both basal glutathione (GSH) concentrations and the H2O2-mediated decreases in GSH were similar in adult and senescent ventricular preparations, as were activities of glutathione peroxidase and glutathione reductase. These observations suggest that interventions known to increase cytoplasmic calcium can amplify age-related impairments of cardiac relaxation through mechanisms that may be independent of the glutathione pathway.