Perna A F, Smogorzewski M, Massry S G
Division of Nephrology, University of Southern California, Los Angeles.
Kidney Int. 1989 Sep;36(3):453-7. doi: 10.1038/ki.1989.216.
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 beta-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 on 45Ca 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 less than 0.01) reduction in the oxidation of LCFA and SCFA by and of CPT activity of myocardial mitochondria and a significant increase in 45Ca 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 myocardiopathy.
在慢性肾衰竭（CRF）中，由于肉碱棕榈酰转移酶（CPT）活性降低以及线粒体基质中β-氧化序列中的酶活性降低，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（PTH）通过增加钙进入细胞的能力，增强心肌对钙的摄取，导致钙积累，进而影响线粒体功能。因此，钙通道阻滞剂可能纠正这些紊乱。本研究考察了维拉帕米对LCFA和SCFA氧化、心肌线粒体CPT活性、以及对从CRF大鼠和接受PTH治疗的大鼠获取的心肌的45Ca摄取和钙含量的影响，这些大鼠分别给予或未给予维拉帕米。给予PTH四天和CRF 21天均导致心肌线粒体对LCFA和SCFA的氧化以及CPT活性显著降低（P<0.01），同时心肌的45Ca摄取和钙含量显著增加。同时给予维拉帕米可逆转所有这些紊乱。单独给予正常大鼠维拉帕米4天或21天，这些参数未发生显著变化。我们的研究结果与以下观点一致，即CRF或PTH治疗后心肌对LCFA和SCFA氧化的改变与PTH诱导的心脏钙积累有关，并且可以被钙通道阻滞剂逆转。这些数据可为尿毒症心肌病的治疗提供一种合理的治疗方法。
