Angiotensin II receptor blockers improve endothelial dysfunction associated with sympathetic hyperactivity in metabolic syndrome.
OBJECTIVE
Renin-angiotensin system inhibitors are preferred for the treatment of hypertension with metabolic syndrome (MetS). Underlying endothelial dysfunction and sympathetic nervous system (SNS) activation are critically involved in the pathogenesis of hypertension in MetS. We investigated whether treatment with angiotensin II type 1 receptor blockers (ARBs) improves endothelial and autonomic function in patients with MetS.


RESULTS
We conducted a prospective, randomized, open-label, blinded endpoint trial. Sixty patients with MetS were randomized into three treatment groups: telmisartan, candesartan, or diet therapy (control; n = 20 each), and treated for 6 months. To evaluate the endothelial function of forearm resistance arteries, blood flow and vascular resistance were measured using a strain-gauge plethysmograph during intra-arterial infusion of acetylcholine (ACh) or sodium nitroprusside (SNP). At 6 months, both telmisartan and candesartan comparably decreased blood pressure. Furthermore, ARB treatment ameliorated impaired forearm vasodilation in response to ACh. Telmisartan had a greater effect than candesartan on ACh-induced forearm vasodilation. In contrast, forearm vasodilation in response to SNP was comparable between the telmisartan and candesartan-treated groups. ARB treatment increased high-molecular-weight (HMW) adiponectin levels and baroreflex sensitivity, but telmisartan had a stronger effect than candesartan. In addition, only telmisartan treatment significantly decreased plasma norepinephrine concentrations, blood pressure variability, and heart rate variability based on spectral analysis.


CONCLUSIONS
These findings indicate that ARBs improve impaired endothelial and baroreflex function, and increase HMW adiponectin levels in patients with MetS. Telmisartan exhibited more beneficial effects than candesartan, and only telmisartan reduced sympathetic hyperactivity, despite similar depressor effects.
Department of Advanced Therapeutics for Cardiovascular Diseases, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Takuya
T
Kishi
Yoshitaka
Y
Hirooka
Satomi
S
Konno
Kenji
K
Sunagawa
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004035:Diet Therapy; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D008875:Middle Aged; D011446:Prospective Studies; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D000077333:Telmisartan; D013777:Tetrazoles / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan; D000077333:Telmisartan