Combined Effects of Enalapril and Spironolactone in Hamsters With Dilated Cardiomyopathy

Abstract

Chronic angiotensin I-converting enzyme inhibition can be associated with aldosterone escape. We investigated the effects of enalapril, spironolactone, and their combination on hemodynamics and cardiac remodeling in cardiomyopathic hamsters to determine whether these drugs could exert additive effects. Cardiomyopathic hamsters, Bio TO-2 dilated strain, were orally treated with enalapril (20 mg. kg. day ) and/or spironolactone (20 mg. kg. day ) according to a 2 x 2 factorial design from 120 days of age. Animals were investigated at 180 (10 animals per group) and 240 (16 animals per group) days of age. Compared with corresponding untreated groups, enalapril significantly decreased mean blood pressure (-18%); enalapril and spironolactone significantly increased cardiac output (+28%, +11%) and femoral blood flow (+10%, +12%) and significantly decreased systemic (-38%, -17%) and femoral (-26%, -13%) vascular resistances. Enalapril and spironolactone significantly decreased left ventricle cavity area (-21%, -26%) and left (-34%, -47%) and right (-37%, -48%) ventricle collagen density. Spironolactone significantly increased left ventricle wall thickness (+4%). There were significant enalapril x spironolactone interactions for most variables (compared with control group, +52%, +36%, +45% for cardiac output; +26%, +28%, +26% for femoral blood flow; -50%, -30%, -45% for systemic vascular resistance; -33%, -20%, -35% for femoral vascular resistance; -27%, -31%, -40% for left ventricle cavity area; and -46%, -58%, -60% for left and -39%, -50%, -66% for right ventricle collagen density in enalapril, spironolactone, and enalapril + spironolactone groups, respectively). In cardiomyopathic hamsters, enalapril and spironolactone in combination did not improve hemodynamics more than enalapril alone but induced stronger effects than each drug alone on cardiac remodeling.

Cardiomyopathic Syrian Hamster as a Model of Congestive Heart Failure

“…This lack of effect on left ventricle wall thickness could result from the fact that the reduction of chamber dilation (which should have increased left ventricle wall thickness) was compensated by the regression of fibrosis (which would decrease left ventricle wall thickness). The left ventricle dilation and collagen density reductions induced by enalapril are consistent with the effects described in the literature with ACE inhibitors (Watanabe et al, ; Goineau et al, ).…”

“…Enalapril also tended to decrease the left ventricular end diastolic blood pressure (10 ± 0 mmHg versus 12 ± 1 mmHg in the vehicle control group, NS). It also significantly reduced the dP/dt max (2700 ± 170 versus 3689 ± 136 mmHg/sec in the vehicle control group, p <0.001) and the mean, systolic and diastolic (Narita et al, 1996;Ryoke et al, 1999;Goineau et al, 2003). The effects of enalapril on organ weight are shown in Table 5.50.1.…”

Chronic Administration of Carvedilol Improves Cardiac Function in 6-Month-Old Syrian Cardiomyopathic Hamsters

“…Overactivation of this system in the adult SCH heart has been implicated in the decline of right ventricular conduction velocity and in the development of morphological abnormalities [30] . Moreover, the AT-1 receptor blocker losartan prevents an increased heart-tobody mass ratio in 5-month-old SCH [26] , and the angiotensin-converting-enzyme inhibitor enalapril increases CO in adult SCH [31] . The role of the sympathetic system in SCH cardiomyopathy, however, is not clearly established.…”

Rescue of familial cardiomyopathies by modifications at the level of sarcomere and Ca2+ fluxes

“…ACE inhibition using enalapril alone, or in association with the mineralocorticoid receptor antagonist spironolactone, decreased LV cavity size and collagen density in cardiomyopathic hamsters [157, 158]. It has also been shown that aldosterone and aldosterone synthase mRNA levels are elevated in humans with FHC [153].…”