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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Ruzicka
Marcel
M
Hypertension Unit H360, University of Ottawa Heart Institute, University of Ottawa, 40 Ruskin Street, Ottawa, Ontario, Canada K1Y 4W7. mruzicka@ottawahospital.on.ca
Coletta
Elizabeth
E
Floras
John
J
Leenen
Frans H H
FH
D000328:Adult; D000367:Age Factors; D000368:Aged; D000804:Angiotensin II / Q000097:blood; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage*; D009638:Norepinephrine / Q000097:blood; D012083:Renin / Q000097:blood; D013564:Sympathetic Nervous System / Q000187:drug effects*
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D000804:Angiotensin II; D012083:Renin; D009543:Nifedipine; D009638:Norepinephrine