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 /sup 45/Ca 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 /sup 45/Ca 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.
- Research Organization:
- Univ. of Southern California, Los Angeles (USA)
- OSTI ID:
- 6497077
- Journal Information:
- Kidney Int.; (United States), Vol. 34:6
- Country of Publication:
- United States
- Language:
- English
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CARBOXYLIC ACIDS
METABOLISM
TRANSFERASES
ENZYME ACTIVITY
UROGENITAL SYSTEM DISEASES
PATHOGENESIS
VASODILATORS
BIOLOGICAL EFFECTS
CALCIUM 45
KIDNEYS
MITOCHONDRIA
MUSCLES
RATS
TRACER TECHNIQUES
ALKALINE EARTH ISOTOPES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CALCIUM ISOTOPES
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ENZYMES
EVEN-ODD NUCLEI
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
RADIOISOTOPES
RODENTS
VERTEBRATES
550901* - Pathology- Tracer Techniques