Comparison of vasculoprotective effects of benidipine and losartan in a rat model of metabolic syndrome.
Although antihypertensive drugs confer improvement in endothelial dysfunction and protection from atherogenesis in hypertension, different classes of antihypertensive drugs may elicit different degrees of vasculoprotective effects. We have investigated the effects of a long-acting calcium antagonist, benidipine, and an angiotensin AT(1) receptor antagonist, losartan, on the vascular damage observed in OLETF rats, an animal model of metabolic syndrome. At 34 weeks of age, OLETF rats were treated with either benidipine (3 mg/kg/day, per os) or losartan (25 mg/kg/day, per os) for 8 weeks. The extent of blood pressure reduction, restoration endothelium-dependent aortic relaxation, and elevation of serum nitrite/nitrate concentration did not differ significantly between benidipine- and losartan-treated OLETF rats. Benidipine and losartan also reduced the aortic expression of transforming growth factor-beta1 mRNA and thickening of the vascular wall to a similar extent. Increased cardiac fibrosis was also inhibited by both benidipine and losartan. These data suggest that, when used in an antihypertensive dose, benidipine is as effective as losartan in restoring vascular endothelial function and in suppressing of cardiovascular remodeling in an animal model of metabolic syndrome.
Matsuzaki
Gen
G
Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Japan.
Ishizaka
Nobukazu
N
Furuta
Kyoko
K
Hongo
Makiko
M
Saito
Kan
K
Sakurai
Ryota
R
Koike
Kazuhiko
K
Nagai
Ryozo
R
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000473:pathology*; D005355:Fibrosis; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D019808:Losartan / Q000627:therapeutic use*; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000473:pathology*; D009126:Muscle Relaxation / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020334:Rats, Inbred OLETF; D020133:Reverse Transcriptase Polymerase Chain Reaction
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; C061004:benidipine; D019808:Losartan