Effects of verapamil on the abnormalities in fatty acid oxidation of myocardium.
Effects of verapamil on the abnormalities in fatty acid oxidation of myocardium.
复制标题
维拉帕米对心肌脂肪酸氧化异常的影响。
DOI：
10.1038/ki.1989.216
复制
发表时间：
1989
影响因子：
19.6
通讯作者：
Massry,SG
中科院分区：
文献类型：
--
作者：
Perna,AF;Smogorzewski,M;Massry,SG
维拉帕米对心肌脂肪酸氧化异常的影响。由于肉碱棕榈酰转移酶（CPT）和线粒体基质中β-氧化序列酶的活性降低，心肌线粒体对长链脂肪酸（LCFA）和短链脂肪酸（SCFA）的氧化受到损害。有人提出，甲状旁腺激素通过其增加钙进入细胞的能力，增强心肌对钙的吸收，导致钙积累，进而影响线粒体功能。因此，钙通道阻滞剂可以纠正这些紊乱。本研究检测了维拉帕米对心肌线粒体LCFA和SCFA氧化的影响，对心肌线粒体CPT活性的影响，以及对CRF大鼠和PTH治疗大鼠心肌45ca摄取和钙含量的影响。PTH给药4 d和CRF给药21 d均显著（P < 0.01）降低心肌线粒体LCFA和SCFA氧化及CPT活性，显著增加心肌对45ca的摄取及含量。同时服用维拉帕米逆转了所有这些紊乱。正常大鼠单独给药维拉帕米4天或21天没有引起这些参数的显著变化。我们的研究结果与CRF或PTH治疗后心肌LCFA和SCFA氧化的改变与PTH诱导的心脏钙积累有关，并且可以通过钙通道阻滞剂逆转。本研究结果可为尿毒症心肌病的合理治疗提供依据。
Effects of verapamil on the abnormalities in fatty acid oxidation of myocardium. The oxidation of long (LCFA) and short chain fatty acids (SCFA) by myocardial mitochondria is impaired in CRF due to reduced activity of carnitine palmitoyl transferase (CPT) and of enzymes in the β-oxidation sequence in mitochondrial matrix. It was proposed that PTH, through its ability to augment entry of calcium into cells, enhances calcium uptake by the myocardium leading to calcium accumulation which in turn affects mitochondrial function. A calcium channel blocker may therefore correct these derangements. The present study examined the effects of verapamil on LCFA and SCFA oxidation and on CPT activity of myocardial mitochondria and on45Ca uptake by, and calcium content of, myocardium obtained from CRF rats and rats treated with PTH, with and without administration of verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P < 0.01) reduction in the oxidation of LCFA and SCFA by and of CPT activity of myocardial mitochondria and a significant increase in45Ca uptake by, and content of, the myocardium. Simultaneous administration of verapamil reversed all these derangements. Administration of verapamil alone to normal rats for 4 or 21 days did not cause significant changes in these parameters. The results of our studies are consistent with the notion that the alterations in myocardial oxidation of LCFA and SCFA in CRF or after PTH treatment are related to PTH-induced calcium accumulation in the heart, and could be reversed by a calcium channel blocker. The data could provide a rational therapeutic approach for the management of uremic myocardi-opathy.