Effect of Carvedilol on Cardiovascular Status of 2‐month‐old Syrian Cardiomyopathic Hamsters

Abstract

Heart failure (HF) is a multifactorial and progressive disease that has been linked to activation of the renin-angiotensin (RAS) and the sympathetic systems. In recent years, beta-blockers have been shown to improve the status of HF patients, although the precise mechanisms are still unclear. The present study evaluates the effect of beta-blockade on cardiac and vascular function of 2-month-old Syrian cardiomyopathic hamsters (SCH) after treatment for a 4-week period with carvedilol (1mg/kg/d). At this stage cardiac function is preserved but vascular abnormalities exist, including endothelial dysfunction. Echocardiographic studies, which included stroke volume (SV), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), ejection fraction (EF), cardiac output (CO), cardiac output index (COI), heart rate (HR), and left ventricular posterior wall thickness (LVPWT) were evaluated. Systolic blood pressure (SBP), and contractile responses of aortic rings to angiotensin II (Ang II) and norepinephrine (NE) were also determined. Age-matched golden hamsters were used as controls. In SCH, carvedilol administration decreases SBP from 107 to 77 mmHg, (n= 5, P<0.05), reduces body weight by 8 % (n=5, P<0.05), and increases the contractile response of aortic rings to Ang II from 0.83 to 1.23g (n=9, P<0.05). SV, CO, HR, COI, EF, LVESV, LVEDV, LVPWT, and the contractile response to NE, however, were unchanged. These results suggest that carvedilol improves vascular function in 2-month-old SCH without compromising cardiac function. Supported by Grant 2 SO6 GM08224 MBRS-SCORE.