Effects of prazosin on hemodynamics, hemostasis, and serum lipid and lipoprotein levels in normal and hypercholesterolemic monkeys

Abstract

The effect of prazosin on hemodynamics, hemostasis, and serum lipid and lipoprotein levels was investigated in normal and hypercholesterolemic rhesus ( Macaca mulatta) and cynomolgus ( Macaca fascicularis) monkeys. Administration of prazosin (2 mg/kg bodyweight, orally, twice a day) for three weeks caused significant reductions in plasma cholesterol, including low- plus very low-density lipoprotein cholesterol, apolipoprotein B, and triglyceride levels. Drug therapy was associated with increased high-density lipoprotein cholesterol levels, although in one group of monkeys this rise also was associated with a reduction in apolipoprotein A 1. Prazosin treatment significantly decreased mean arterial pressure in normal and hypercholesterolemic monkeys. As was expected, acute administration of phenylephrine caused mean arterial pressure to rise, with animals receiving normal- or high-cholesterol-containing diets showing similar responses. After prazosin treatment, however, a greater inhibition in the phenylephrine pressor response was observed in hypercholesterolemic monkeys compared with normal animals. Platelet aggregation in response to adenosine 5′-diphosphate, prothrombin time, and activated partial thromboplastin time were not altered by prazosin. Thus, in our nonhuman primate models of hypercholesterolemia, administration of prazosin resulted in reduction in lipid and apoprotein levels with no change in hemostasis.