Animal model and therapeutic prospects for left ventricular hypertrophy and associated renal complication

Abstract

Cardiac and renal dysfunction often co-occur and considerably worsen the prognosis leading to difficulty in therapy in left ventricular hypertrophy (LVH). The aim of this study was to elucidate changes in expression of human ortholog genes of hypertension, vascular and cardiac remodeling and hypertensive nephropathy phenotypes under normal, disease and gasotransmitter, H 2 S (hydrogen sulphide) and NO (nitric oxide) and combined (H 2 S+NO), treatment of rat myocardium and renal tissues. LVH rat models were generated and were treated with H 2 S and NO. Relative gene expression was quantified. Heart and renal physical indices were significantly modified under individual as well as combined H 2 S+NO treatment in control and LVH rats. Expression analysis revealed, hypertension, vascular remodeling genes ACE, TNFα and IGF1, mRNAs to be significantly increased (P<0.05) in myocardia and kidneys of LVH rats, while individual and combined H 2 S+NO treatment reduced gene expression to normal/near to normal values. The cardiac remodeling genes MYH7, TGFβ, SMAD4 and BRG1 expression were significantly up-regulated (P<0.05) in the myocardia of LVH and combined H 2 S+NO treatment, which recovered the normal/near to normal expression more effectively as compared to individual treatments. Interestingly, individual as well as combined H 2 S and NO treatment significantly decreased PKD1 expression in renal tissue, which was significantly up-regulated in LVH rats (P<0.05). The reduction in hemodynamic parameters and cardiac indices as well as alteration in gene expression on treatment in LVH rat model indicates important therapeutic potential of combined treatment with H 2 S+NO gasotransmitters in hypertension and cardiac hypertrophy associated with renal complications.