AT1 receptor antagonism improves endothelial dysfunction in postmenopausal women.
The menopause is associated with an increased incidence of atherosclerotic disease. Estrogen deficiency causes AT1 receptor overexpression which is involved in the development of vascular dysfunction. The effect of a 6 week-treatment with the AT1 receptor antagonist candesartan (16 mg/d) on endothelium-dependent vasorelaxation was compared to the treatment with placebo or the calcium channel antagonist felodipine (5 mg/d) in 29 postmenopausal women in the absence or presence of hormone replacement therapy (HRT) in a prospective, double-blind, randomized cross-over study. Endothelial function was assessed by measurement of forearm blood flow (FBF) by venous occlusion plethysmography. FBF during reactive hyperemia was significantly improved by candesartan in patients without HRT (hyperemic peak flow and area under the FBF curve), whereas felodipine and placebo exerted no effect. In patients with HRT, no treatment regimen showed a significant effect on endothelial function. Nitroglycerin-induced vasorelaxation and basal FBF were not significantly altered in all groups. AT1 receptor antagonism improves vascular function in postmenopausal women without HRT. Thus, AT1 receptor blockade may resemble an efficient approach for the prevention of vascular dysfunction in estrogen-deficient women.
Wassmann
Kerstin
K
Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
Ghiassi
Ardeshir
A
Wassmann
Sven
S
Böhm
Michael
M
Nickenig
Georg
G
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D050197:Atherosclerosis / Q000517:prevention & control; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001783:Blood Flow Velocity / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004967:Estrogens / Q000172:deficiency; D015736:Felodipine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005542:Forearm; D006801:Humans; D008875:Middle Aged; D010991:Plethysmography; D017698:Postmenopause; D011446:Prospective Studies; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D004967:Estrogens; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D015736:Felodipine; C081643:candesartan