ANTIHYPERTENSIVE EFFECT OF FELODIPINE ASSOCIATED WITH PERSISTENT SYMPATHETIC ACTIVATION AND MINIMAL REGRESSION OF LEFT-VENTRICULAR HYPERTROPHY

Twenty patients whose systemic hypertension was not controlled with chronic beta-blocker therapy were studied to evaluate the acute (first dose), short-term (4 weeks) and chronic (6 to 12 months) effects of the calcium antagonist felodipine on blood pressure (BP), left ventricular (LV) anatomy and function and on plasma norepinephrine. The first dose of felodipine rapidly reduced total peripheral resistance and BP, associated with significant increases in heart rate, cardiac output and plasma norepinephrine. During chronic therapy, at the end of the dosing interval (12 hours), significant decreases in BP persisted with minimal changes in the other variables. However, even after 1 year of therapy BP after dosing again rapidly decreased associated with 50 to 100% increases in plasma norepinephrine and small increases in heart rate and cardiac output. Despite the marked decreases in systolic BP, LV wall thickness and mass showed only small decreases (LV mass - 17 +/- 7 g/m2 after 1 year) and significant LV hypertrophy persisted after 1 year. Both average systolic BP and plasma norepinephrine were significant determinants of LV mass over the duration of the study. It is concluded that during chronic treatment with the twice-daily tablet formulation of felodipine, major daily fluctuations in BP persist associated with persisting sympathetic hyperactivity. The latter may play a role in the modest regression of LV hypertrophy despite 30 to 40 mm Hg decreases in systolic BP for 1 year.