Angiotensin II type 1 receptor blocker attenuates exacerbated left ventricular remodeling and failure in diabetes-associated myocardial infarction.
Diabetes mellitus adversely affects the outcomes in patients with myocardial infarction (MI), due in part to the exacerbation of left ventricular (LV) remodeling. Although angiotensin II type 1 receptor blocker (ARB) has been demonstrated to be effective in the treatment of heart failure, information about the potential benefits of ARB on advanced LV failure associated with diabetes is lacking. To induce diabetes, male mice were injected intraperitoneally with streptozotocin (200 mg/kg). At 2 weeks, anterior MI was created by ligating the left coronary artery. These animals received treatment with olmesartan (0.1 mg/kg/day; n = 50) or vehicle (n = 51) for 4 weeks. Diabetes worsened the survival and exaggerated echocardiographic LV dilatation and dysfunction in MI. Treatment of diabetic MI mice with olmesartan significantly improved the survival rate (42% versus 27%, P < 0.05) without affecting blood glucose, arterial blood pressure, or infarct size. It also attenuated LV dysfunction in diabetic MI. Likewise, olmesartan attenuated myocyte hypertrophy, interstitial fibrosis, and the number of apoptotic cells in the noninfarcted LV from diabetic MI. Post-MI LV remodeling and failure in diabetes were ameliorated by ARB, providing further evidence that angiotensin II plays a pivotal role in the exacerbated heart failure after diabetic MI.
Matsusaka
Hidenori
H
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kinugawa
Shintaro
S
Ide
Tomomi
T
Matsushima
Shouji
S
Shiomi
Tetsuya
T
Kubota
Toru
T
Sunagawa
Kenji
K
Tsutsui
Hiroyuki
H
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D004452:Echocardiography; D008297:Male; D045726:Metalloproteases / Q000378:metabolism; D051379:Mice; D009203:Myocardial Infarction / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D013311:Streptozocin / Q000494:pharmacology; D015996:Survival Rate; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D001786:Blood Glucose; D044140:Receptor, Angiotensin, Type 1; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D013311:Streptozocin; D045726:Metalloproteases