Verapamil Prevents Chronic Renal Failure-Induced Abnormalities in Lipid Metabolism

Abstract

Hypertriglyceridemia is common in chronic renal failure (CRF); this derangement is due to decreased peripheral removal of triglycerides. Certain data indicate that the state of secondary hyperparathyroidism of CRF is, at least in part, responsible for derangements in lipid metabolism. It has been proposed that chronic excess of parathyroid hormone exerts its deleterious effects on many organs through its ability to raise basal levels of cytosolic calcium. Prevention of the latter by a calcium channel blocker is followed by the correction of organ dysfunctions. The present study examined the effect of treatment of CRF rats with verapamil on several parameters of lipid metabolism. Chronic renal failure rats displayed hypertriglyceridemia, fat intolerance, reduced postheparin plasma lipoprotein and hepatic lipase activities, decreased hepatic lipase in liver homogenate, and elevated calcium content in liver and epididymal fat. Treatment of the CRF rats with verapamil prevented all these derangements in lipid metabolism. These effects of verapamil were similar to those produced by parathyroidectomy of CRF rats. The data are consistent with the formulation that chronic excess of parathyroid hormone increases the calcium burden of liver and adipose tissue and consequently impairs the synthesis and/or release of lipoprotein and hepatic lipases. Reduced availability of these enzymes in plasma results in impared peripheral removal of triglycerides, leading to hypertriglyceridemia.