Effect of gasotransmitters treatment on expression of hypertension, vascular and cardiac remodeling and hypertensive nephropathy genes in left ventricular hypertrophy

Abstract

Background: Cardiac and renal dysfunction are often co-morbid pathologies leading to worsening prognosis resulting in difficulty in therapy of left ventricular hypertrophy (LVH). The aim of the current study was to determine the changes in expression of human ortholog genes of hypertension, vascular and cardiac remodeling and hypertensive nephropathy phenotypes under normal, disease and upon treatment with gasotransmitter including H₂S (hydrogen sulphide), NO (nitric oxide) and combined (H₂S + NO).

Methods: A total of 72 Wistar Kyoto rats (with equivalent male and female animals) were recruited in the present study where LVH rat models were treated with H₂S and NO individually as well as with both combined. Cardiac and renal physical indices were recorded and relative gene expression were quantified.

Results: Both cardiac and renal physical indices were significantly modified with individual as well as combined H₂S + NO treatment in control and LVH rats. Expression analysis revealed, hypertension, vascular remodeling genes ACE, TNFα and IGF1, mRNAs to be significantly higher (P ≤ 0.05) in the myocardia and renal tissues of LVH rats, while individual and combined H₂S + NO treatment resulted in lowering the gene expression to normal/near to normal levels. The cardiac remodeling genes MYH7, TGFβ, SMAD4 and BRG1 expression were significantly up-regulated (P ≤ 0.05) in the myocardia of LVH where the combined H₂S + NO treatment resulted in normal/near to normal expression more effectively as compared to individual treatments. In addition individual as well as combined H₂S and NO treatment significantly decreased PKD1 expression in renal tissue, which was up-regulated in LVH rats (P ≤ 0.05).

Conclusions: The reduction in hemodynamic parameters and cardiac indices as well as alteration in gene expression on treatment of LVH rat model indicates important therapeutic potential of combined treatment with H₂S + NO gasotransmitters in hypertension and cardiac hypertrophy when present as co-morbidity with renal complications.

Keywords: Cytoprotection; Gasotansmitters; Left ventricular hypertrophy; Therapeutics.