Effects of doxazosin on lipids, lipoprotein lipases, and cholesterol synthesis in the golden hamster

Abstract

The effects of treatment with adrenoceptor blockers on sites regulating lipid metabolism were studied in golden hamsters. In hamsters fed a standard chow, doxazosin, propranolol, and atenolol did not affect plasma cholesterol or triglycerides. After hypercholesterolemia was induced by feeding a cholesterol-enriched diet, doxazosin lowered plasma cholesterol by 12%. Lipoprotein lipase activity in adipose tissue and in the heart was not changed by any of the treatments. Hepatic lipase activity in the liver and blood was lowered by 31% in the doxazosin-treated animals. Hepatic cholesterol synthesis, measured as acetate incorporation into cholesterol and hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity, was also lowered in the doxazosin-treated hamsters. After norepinephrine administration to cholesterol-fed hamsters, atenolol increased (+8%) and doxazosin decreased (-35%) plasma triglycerides. Plasma cholesterol levels and hepatic cholesterol synthesis were no longer significantly affected by doxazosin. In norepinephrine-treated animals, adipose tissue lipoprotein lipase activity was enhanced (+30%) by doxazosin. Hepatic lipase activity in plasma and liver, which was lowered by norepinephrine, was increased by doxazosin. In hamsters not treated with norepinephrine, adrenoceptor blockers had no effect on plasma insulin or thyroid hormone, but with norepinephrine, levels of both insulin and thyroid hormone were increased by doxazosin. These data indicate that selective alpha 1-inhibition with doxazosin may interfere with lipid metabolism at several regulatory sites. The effects depend to a large extent on nutritional and hormonal status. Doxazosin might exert these effects partly via influences on other hormones.