Acute systemic and regional hemodynamic effects of felodipine, a new calcium antagonist, in conscious renal hypertensive rabbits.

Abstract

Using the radioactive microsphere technique, we studied the acute systemic and regional hemodynamic effects of felodipine (10, 30, and 100 nmol/kg, i.v.) in conscious renal hypertensive rabbits. A dose-dependent decrease in arterial blood pressure was observed after felodipine administration, accompanied by tachycardia. Cardiac output increased significantly after the third felodipine dose. Thus, the hypotensive effect of the drug resulted from a reduction in total peripheral resistance. An increase in blood flow to the heart was measured after felodipine. However, probably secondary to the reduction in diastolic perfusion time, a decrease in the endocardial/epicardial blood flow ratio was noticed in the left ventricular wall. The drug also enhanced the blood supply to the brain, the gastrointestinal tract, and, at higher doses, to the skeletal muscles while blood flow to the kidneys and the bones remained unchanged. After the highest dose of felodipine, a significant decrease in the blood flow to the skin was measured. With the exception of the cutaneous vascular bed, felodipine caused a rather generalized peripheral vasodilatation. In conclusion, felodipine appears to be a very effective antihypertensive agent. However, the stimulation of the heart and the unfavorable regional blood flow distribution in the left ventricular wall illustrate the negative aspects of single treatment with this arterial vasodilator.