Perna A F, Smogorzewski M, Massry S G
Division of Nephrology, University of Southern California, Los Angeles.
Kidney Int. 1988 Dec;34(6):774-8. doi: 10.1038/ki.1988.248.
Chronic renal failure (CRF) is associated with impaired long chain fatty acids (LCFA) oxidation by skeletal muscle mitochondria. This is due to reduced activity of carnitine palmitoyl transferase (CPT). These derangements were attributed to the secondary hyperparathyroidism of CRF, since prior parathyroidectomy in CRF rats reversed these abnormalities and PTH administration to normal rats reproduced them. It was proposed that these effects of PTH are mediated by its ionophoric property leading to increased entry of calcium into skeletal muscle. A calcium channel blocker may, therefore, correct these derangements. The present study examined the effects of verapamil on LCFA oxidation, CPT activity by skeletal muscle mitochondria, and 45Ca uptake by skeletal muscle obtained from CRF rats and normal animals treated with PTH with and without verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P less than 0.01) reduction in LCFA oxidation and CPT activity of skeletal muscle mitochondria, and significant (P less than 0.01) increment in 45Ca uptake by skeletal muscle. Simultaneous treatment with verapamil corrected all these derangements. Administration of verapamil alone to normal rats did not cause a significant change in any of these parameters. The data are consistent with the proposition that the alterations in LCFA in CRF or after PTH treatment are related to the ionophoric action of the hormone and could be reversed by a calcium channel blocker.
慢性肾衰竭（CRF）与骨骼肌线粒体长链脂肪酸（LCFA）氧化受损有关。这是由于肉碱棕榈酰转移酶（CPT）活性降低所致。这些紊乱归因于CRF的继发性甲状旁腺功能亢进，因为CRF大鼠先前进行甲状旁腺切除可逆转这些异常，而向正常大鼠注射甲状旁腺激素（PTH）则会重现这些异常。有人提出，PTH的这些作用是由其离子载体特性介导的，导致钙进入骨骼肌的量增加。因此，钙通道阻滞剂可能会纠正这些紊乱。本研究考察了维拉帕米对CRF大鼠以及接受PTH治疗的正常动物（无论是否使用维拉帕米）的骨骼肌中LCFA氧化、骨骼肌线粒体CPT活性以及45Ca摄取的影响。给予PTH四天以及CRF 21天均使骨骼肌线粒体的LCFA氧化和CPT活性显著降低（P<0.01），并使骨骼肌的45Ca摄取显著增加（P<0.01）。同时用维拉帕米治疗可纠正所有这些紊乱。单独给正常大鼠施用维拉帕米不会使这些参数中的任何一个发生显著变化。这些数据与以下观点一致，即CRF或PTH治疗后LCFA的改变与该激素的离子载体作用有关，并且可以被钙通道阻滞剂逆转。
