Effects of the calcium antagonist felodipine on the sympathetic and renin-angiotensin-aldosterone systems in essential hypertension.
Studies were performed in 10 male patients with untreated essential hypertension, WHO grade I-II, aged 25-62 years, to explore the acute (single dose) and long-term (8 weeks) effects of felodipine on sympathetic activity--evaluated by plasma and urinary catecholamines--as related to blood pressure, heart rate and the activity in the renin-angiotensin-aldosterone system. The patients were hospitalized for 8 (acute) and 6 (long-term) days and were maintained on a standardized daily intake of sodium (150 mmol), potassium (75 mmol) and water (2,500 ml). Acute felodipine administration (10 mg) significantly reduced blood pressure and increased heart rate. Plasma and urinary noradrenaline, plasma renin activity and angiotensin II increased, whereas plasma and urinary adrenaline, dopamine, aldosterone and plasma vasopressin were unaltered. Long-term felodipine treatment, 10 mg twice daily, reduced blood pressure to a similar extent as acute felodipine administration, but heart rate was not significantly changed. Plasma noradrenaline 3 and 12 hours after the last dose and urinary noradrenaline were increased, whereas plasma and urinary adrenaline and dopamine were unchanged. Plasma renin activity and angiotensin II were increased 3 hours, but unchanged 12 hours after the last dose. Plasma aldosterone was unchanged but urinary aldosterone increased. Plasma vasopressin was unchanged. The changes in plasma noradrenaline as related to blood pressure, heart rate, plasma renin activity and angiotensin II during long-term felodipine treatment may reflect decreased cardiac and renal beta-adrenoceptor-mediated responses. Increased renal clearance of aldosterone could partly explain the unaltered plasma aldosterone level in spite of increased plasma angiotensin II following long-term felodipine treatment.
Katzman
P L
PL
Department of Endocrinology, Lund University Clinics, General Hospital, Malmö, Sweden.
Hulthén
U L
UL
Hökfelt
B
B
D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D015736:Felodipine; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009568:Nitrendipine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013997:Time Factors
D000959:Antihypertensive Agents; D002395:Catecholamines; D009568:Nitrendipine; D015736:Felodipine