The Long-Acting Ca2+-Channel Blocker Azelnidipine Prevents Left Ventricular Remodeling After Myocardial Infarction

Abstract

Abstract. Long-acting Ca 2+-channel blockers have been reported to be effective in treating ischemic heart disease. However, their effects on cardiac remodeling after myocardial infarction (MI) are still unclear. We performed this study to examine the effect of azelnidipine on left ventricular (LV) remodeling, including systolic and diastolic dysfunction, in rats with MI. MI was induced by ligation of the left anterior descending artery. The rats were then separated into 3 groups: a sham-operated group (n = 9), untreated MI group (n = 10), and azelnidipine-treated MI group (n = 10). Four weeks after MI, hemodynamic measurements and Doppler echocardiographic assessment were performed. LV weight and LV end-diastolic dimension were significantly higher in the untreated MI group than in the sham-operated group. Azelnidipine significantly prevented the increases in these parameters. Azelnidipine also improved the ejection fraction (42 ± 3%, P<0.05) and the E wave to A wave ratio (3.2 ± 0.5, P<0.05), compared with the untreated MI group (31 ± 3% and 5.3 ± 0.8, respectively). In conclusion, azelnidipine can prevent LV remodeling and improve systolic and diastolic function after MI. Administration of long-acting Ca 2+-channel blockers after MI is an effective strategy for treating MI.

Azelnidipine protects myocardium in hyperglycemia-induced cardiac damage

“…Despite some controversy in the past [49], large patient studies have demonstrated that calcium channel blockers are effective in reducing the mortality and morbidity of cardiovascular disease [50,51]. AZL is one of the cardiobeneficial CCB that decreases blood pressure without increasing the heart-rate [33,34], prevents cardiac damage [3], reduce glucose intolerance [52] and possesses antioxidant properties [37]. However, there is a significant gap in our knowledge about the cardioprotective action and efficacy of AZL as the effect of AZL on proinflammatory cytokines and altered lipid profile in either diabetic patients or in experimental models of diabetes has not been studied so far.…”

“…Dyslipidemia, oxidative stress and inflammatory injury are important interrelated factors responsible for the development of cardiomyopathy as they are known to promote the progression of premature atherosclerosis, coronary insufficiency and myocardial infarction [2]. Various studies have correlated that the circulating markers of myocardial damage, pro-inflammatory cytokines, calcium dysregulation, oxidative stress and atherogenic lipids are elevated in diabetic patients [3-10]. …”

“…AZL, a newly developed and commercially used novel long-acting DHP-based calcium antagonist has been reported to be effective in treating ischemic heart disease and cardiac remodeling after myocardial infarction (MI) [3] and reduce blood pressure without increasing the heart rate in patients with hypertension [33,34]. In the experimental animals, AZL revealed anti-atherosclerotic effects independent of its blood pressure-lowering actions [35].…”

Anti-hypertensive azelnidipine preserves insulin signaling and glucose uptake against oxidative stress in 3T3-L1 adipocytes

“…In addition, azelnidipine significantly reduces blood pressure without influencing heart rate. It has been shown that azelnidipine has pleiotropic effects such as the preventive effects on left ventricular remodeling after myocardial infarction and on neuronal damage after stroke and the preventive effects on hypertension and diabetic renal dysfunction [9][10][11][12][13]. Recent reports have suggested that azelnidipine increases serum adiponection levels and ameliorates insulin signaling in human subjects [14,15].…”

Riboflavin Alleviates Cardiac Failure in Type I Diabetic Cardiomyopathy

“…Various studies have reported that the circulating markers of myocardial damage, proinflammatory cytokines, calcium dysregulation, oxidative stress and atherogenic lipids are elevated in diabetic patients. 2–9 …”