Candesartan cilexetil in hypertension: effects of six weeks' treatment on haemodynamics, baroreceptor sensitivity and the renin-angiotensin-aldosterone system.
The effects of the angiotensin II receptor blocker candesartan cilexetil on systemic and forearm haemodynamics and baroreceptor sensitivity were evaluated in this randomized, placebo-controlled, double-blind, crossover study. After a 4-week placebo run-in period, 22 patients with essential hypertension (diastolic blood pressure 100-114 mmHg) were randomized to receive either candesartan cilexetil 16 mg or placebo once daily for 6 weeks. At the end of each period, 24 h after the last dose, invasive haemodynamic assessments were performed. Simultaneously, the plasma renin activity and plasma concentrations of angiotensin II, aldosterone and catecholamines were measured. Compared to placebo, candesartan cilexetil significantly reduced mean arterial pressure by 8 mmHg (95% CI: 2.6; 12.3), while cardiac output, stroke volume and heart rate were unchanged. Forearm vascular resistance was reduced by 1 mmHg x ml(-1) x L x min (CI: 0.3; 2.3). The baroreceptor sensitivity was not influenced, but a change in the set-point was noted. Plasma renin activity and angiotensin II concentrations were increased, while the aldosterone concentration was significantly reduced. Plasma catecholamine concentrations were unaffected. In conclusion, 6 weeks' treatment with candesartan cilexetil 16 mg o.d. induced systemic and forearm vasodilatation and a reduction in blood pressure without compromising cardiac performance. The plasma concentration of aldosterone was reduced.
Fridman
K U
KU
Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. katarina.fridman@hassle.se.astra.com
Wysocki
M
M
Friberg
P R
PR
Andersson
O K
OK
D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000627:therapeutic use; D017704:Baroreflex / Q000187:drug effects; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005542:Forearm / Q000098:blood supply / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008875:Middle Aged; D011355:Prodrugs / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011355:Prodrugs; D013777:Tetrazoles; C077793:candesartan cilexetil