Enalapril and Losartan Are More Effective Than Carvedilol in Preventing Dilated Cardiomyopathy in the Syrian Cardiomyopathic Hamster

Abstract

To assess the role of the renin-angiotensin (RAS) and adrenergic systems in the development and progression of dilated cardiomyopathy in the Syrian cardiomyopathic hamster (SCH), echocardiographic parameters were evaluated in 6-month-old animals after 5 months of treatment with enalapril (25 mg/kg/day) plus losartan (10 mg/kg/day), or with carvedilol (1 mg/kg/day). Cardiac output indexes (COI) increased by 53% after RAS blockade and by 20% after beta-blockade in SCH. Moreover, LVEDV and LVESV decreased 30% and 62%, respectively (P < .05) during RAS blockade, whereas ejection fraction (EF) increased by 48%. By contrast, carvedilol reduced LVESV by only 28% (P < .05) and increased EF by only 15% (P < .05). These results suggest that RAS activation plays a critical role in the development of cardiac dysfunction in SCH and that suppression of RAS may be more effective than beta-blockade in retarding the development of cardiomyopathy in SCH. Owing to timing (pre-heart failure stage) and to the single dose protocol, the implications of this study for human subjects remain to be clarified.

Hemodynamic Alterations in the Coronary Circulation of Cardiomyopathic Hamsters: Age and Ang II–dependent Mechanisms

“…The relevance of RAS in the etiology of cardiomyopathy in the hamster is underlined by recent findings that treatment of CM with enalapril (ACEI) and losartan (ARB) from 1 to 6 months of age, significantly reduces the development of dilated cardiomyopathy 42. This finding together with those of the present study, indicate that prevention of early coronary dysfunction preserves cardiac function in CM.…”

“…The results from these studies were compared with those from similar experiments conducted with untreated 2-month-old CT and CM. The doses of NAC and losartan used were based on previous studies 41–42…”

Pitavastatin-attenuated cardiac dysfunction in mice with dilated cardiomyopathy via regulation of myocardial calcium handling proteins

“…Previous studies also reported that RAS inhibition could attenuate cardiac remodeling and heart failure in hypertensive cardiomyopathy (27,28), dilated cardiomyopathy (29,30) and coronary artery disease (31) via inhibition of PKC signaling pathway (26). It was found that the phospho-PKCb2, but not phospho-PKCa and phospho-PKCb1, was significantly up-regulated by 124.4 % (p < 0.01) in DCM, and significantly down-regulated by 30.2 and 50.0 % (p < 0.01) in DCM+LD and DCM+HD, respectively (Fig.…”

δ-Sarcoglycan-deficient muscular dystrophy: from discovery to therapeutic approaches

“…It is thought that disruption of nNOS renders the muscle more susceptible to focal ischaemia and damage by superoxides [121,122]. That nNOS has a role in vascular dysfunction in δ-sarcoglycanopathy is further evidenced by the observation that drugs which increase myocardial NO (for example, simvastatin, losartan) also improve cardiomyopathy in the hamster [123-125]. …”