Effects of low-dose nifedipine GITS on sympathetic activity in young and older patients with hypertension

Abstract

Dihydropyridines have both sympathoexcitatory and sympathoinhibitory effects. To date, the latter have been characterized only in animals. During chronic treatment with long-acting dihydropyridines, sympathoexcitatory effects mediated via the arterial baroreflex are unlikely. However, increases in plasma angiotensin II in response to dihydropyridines could contribute to increases in sympathetic activity during chronic treatment. Such increases may be less in older than in young patients. We evaluated the effects of 4 weeks of treatment with low-dose nifedipine gastrointestinal therapeutic system (GITS; 20 mg/day) compared with placebo on muscle sympathetic nerve activity and plasma noradrenaline, in relation to changes in plasma renin activity and plasma angiotensin II and blood pressure in young and older patients with mild hypertension. Nifedipine GITS decreased systolic and diastolic blood pressures significantly, by 10 +/- 3 mmHg and 7 +/- 2 mmHg respectively, in older patients (age 67 +/- 2 years), but not in younger patients (age 45 +/- 2 years) (decreases of 1 +/- 3 mmHg and 1 +/- 2 mmHg, respectively). Nifedipine GITS caused only minor changes in plasma renin activity and plasma angiotensin II in young and older patients. Compared with changes in response to placebo (-5.7 +/- 2.4 bursts/min), sympathetic activity was increased significantly by nifedipine GITS in the young patients (2.0 +/- 1.7 bursts/min; P < 0.05), but not in older patients (5.4 +/- 1.3 bursts/min by placebo compared with 4.1 +/- 3.5 bursts/min by nifedipine GITS). We conclude that age-related differences in the response of muscle sympathetic nerve activity (and plasma noradrenaline) to low-dose nifedipine GITS in patients with mild hypertension are unlikely to be mediated by plasma angiotensin II. An increase in sympathetic activity may contribute to the absent blood pressure response in young patients with hypertension.