Systemic and Renal Hemodynamic Effects of Single Oral Doses of Felodipine in Patients with Refractory Hypertension Receiving Chronic Therapy with β-Blockers and Diuretics

Abstract

In 12 patients with primary hypertension (WHO stage 2) inadequately controlled by chronic standard triple therapy, hydralazine was replaced by felodipine, a new vasodilating dihydropyridine derivative, and the acute effects of the drug on central and renal hemodynamics were monitored. Following baseline measurements, an oral solution of felodipine (0.075-0.1 mg/kg) was given. A significant hypotensive response was observed 15 min after intake of felodipine and the maximal response (23% reduction of mean arterial pressure) occurred after 30 min. There was a linear relationship between the changes in mean arterial pressure and log plasma concentration of felodipine. Cardiac output (dye dilution) increased during maximal blood pressure reduction, from 5.3 .+-. 1.0 to 6.6 .+-. 2.4 l/min (P < 0.01), partly because of increased heart rate from 57 .+-. 4 to 65 .+-. 9.1 beats/min (P < 0.01) and partly because of increased stroke volume from 93 .+-. 14 to 104 .+-. 33 ml (P < 0.05). Renal plasma flow (paraaminohippuric acid clearance) increased significantly (P < 0.05) from 343 .+-. 138 to 391 .+-. 154 ml/min, while glomerular filtration rate ([51Cr]EDTA clearance) did not change. Arteriovenous noradrenaline [norepinephrine] difference increased 36% during felodipine therapy, when corrected for blood flow increase. Felodipine is a Ca inhibitor with potent vasodilating properties.