Sympatho-excitatory responses to once-daily dihydropyridines in young versus older hypertensive patients: amlodipine versus felodipine extended release

Abstract

Once-daily dihydropyridines exert both indirect sympatho-excitatory and direct central sympatho-inhibitory effects. Age may affect this balance by influencing blood pressure (BP) or renin responses. We evaluated BP, sympathetic and cardiac responses after the first dose and after 8 weeks of treatment with placebo, amlodipine 5 mg/day or felodipine extended release (ER) 5 mg/day in 29 young (22-50 years) versus 37 older (60-77 years) hypertensive patients, using a double-blind, parallel group design. In the young group, neither dihydropyridine dose decreased BP after the first dose and both caused decreases by 5-10 mmHg after chronic treatment. In the older group, felodipine ER decreased BP rapidly and amlodipine more gradually, and after chronic treatment, systolic BP decreased by 20-25 mmHg. Felodipine ER increased the heart rate by 5-10 bpm after the first dose in both age groups and caused persistent increases in the cardiac index (by 0.2 l/min per square metre) and the ejection fraction only in the older group. Amlodipine did not affect cardiac function in the young, and with chronic dosing decreased the heart rate by 3-5 bpm and the cardiac index by 0.2 l/min per square metre in the older group. In the young hypertensive patients, both dihydropyridines increased plasma norepinephrine (NE) after chronic dosing, with little effect after the first dose. In contrast, in the older group felodipine ER increased plasma NE after the first dose but not with chronic dosing, whereas amlodipine had no effect after the first dose, and after chronic dosing tended to decrease plasma NE. We conclude that age is a major determinant not only of the BP but also of the cardiac and sympathetic responses to once-daily dihydropyridines.