Verapamil reverses PTH- or CRF-induced abnormal fatty acid oxidation in muscle.
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.
Perna
A F
AF
Division of Nephrology, University of Southern California, Los Angeles.
Smogorzewski
M
M
Massry
S G
SG
D000818:Animals; D002132:Calcium Radioisotopes; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D010084:Oxidation-Reduction; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology*
D002132:Calcium Radioisotopes; D005227:Fatty Acids; D010281:Parathyroid Hormone; D014700:Verapamil; D002334:Carnitine O-Palmitoyltransferase