EFFECT OF RENNIN INHIBITORS AND ANGIOTENSIN II RECEPTOR ANTAGONISTS ON LEFT VENTRICULAR HYPERTROPHY IN RENOVASCULAR HYPERTENSIVE RATS
Keywords:
Left ventricular hypertrophy, Renovascular hypertension, Cardiac remodeling, Valsartan, AliskirenAbstract
Objective: Left ventricular (LV) hypertrophy involves numerous structural adaptations that may lead to ventricular dysfunction and eventually, heart failure. Particular emphasis is placed on the molecular mechanisms that govern the development of hypertrophy and may lead to maladaptive structural changes resulting in adverse cardiac events. This study investigates the effectiveness of Valsartan (Val) which is an angiotensinII receptor antagonist and Aliskiren (Ali) which is a direct rennin inhibitor in the treatment of cardiac remodeling resulted from renovascular hypertension, particularly left ventricular hypertrophy, and to address the molecular mechanisms underlying them.
Methods: 24 male albino rats were randomly divided into 4 main groups (n=6 each), normal control rats (N), hypertensive control rats (HC), Val treated hypertensive rats (Val, 8 mg/kg/day orally) and Ali treated hypertensive rats (Ali, 25 mg/kg/day orally).
Results: At the end of 4 weeks HC rats showed enhanced hypertrophic response (higher heart weight/body weight ratio) and dyslipidemia (lower high density lipoprotein "HDL-c" and higher triacyl glycerol "TAG") and a significant deletion of antioxidant enzymes in comparison with N group. The β myosin heavy chain "βMHC", regulator of calcineurin-1 "RCAN1", nuclear factor kappa B "NFκB" and inducible nitric oxide synthase "iNOS" was markedly elevated. While, α myosin heavy chain "αMHC" was markedly decreased as compared with N group. On the other hand Val treated hypertensive rats and Ali treated hypertensive rats showed a significant decrease in heart weight/body weight ratio, improved lipogram pattern and higher levels of antioxidant enzymes. While, cardiac β-MHC, RCAN-1, NFκB and iNOS were significantly decreased as compared with HC group. Both Val treated hypertensive rats and Ali treated hypertensive rats showed a significant increase in α-MHC, compared with HC group
Conclusion: The results reported in this study suggested that chronic untreated hypertension induced a pathological hypertrophy. Administration of the Val or Ali individually exerted beneficial effects regarding the improved lipogram pattern and anti-oxidant enzymes levels, as well as cardiac hypertrophy and highlights the role of Val and Ali as a promising therapeutic strategy for hypertension and LV hypertrophy.
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