Serum Lipids, Lipoproteins, Hemodynamics, and Hemostasis in Doxazosin-Treated Monkeys

Abstract

The effect of doxazosin administration on hemodynamics, hemostasis, and serum lipid and lipoprotein levels was investigated in cynomolgus monkeys (Macaca fascicularis) with diet-induced hypercholesterolemia. Acute administration of doxazosin (1 and 5 mg/kg) reduced resting mean arterial pressure by 20% without affecting heart rate, and completely inhibited the pressor response to phenylephrine. Platelet aggregation, prothrombin time, and activated partial thromboplastin time were not altered by the drug. Long-term doxazosin administration (1, 10, and 20 mg/kg/day) was associated with significant reductions in levels of total serum cholesterol (13%), very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol (14%), and apolipoprotein B (15%) without any significant effects on high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1. A 76% reduction in serum triglycerides, independent of drug level, was also seen in doxazosin-treated monkeys. In monkeys removed from drug treatment, serum cholesterol initially exceeded and then returned to pretreatment levels, whereas serum triglycerides remained low for 3 weeks. In our hypercholesterolemic monkey model, the administration of doxazosin resulted in beneficial changes in lipid and apolipoprotein profiles, hemostasis, and hemodynamics.