Physiological, Pathological and Pharmacological Interactions of Hydrogen Sulphide and Nitric Oxide in the Myocardium of Rats with Left Ventricular Hypertrophy.

Ashfaq Ahmad

doi:10.3390/cimb44010030

Abstract

Left ventricular hypertrophy (LVH) is characterized by increased myocardium thickness due to increased oxidative stress and downregulation of cystathione γ lyase (CSE) endothelial nitric oxide synthase (eNOS). Upregulation of CSE by hydrogen sulphide (H2S) and ENOS by L-arginine can arrest the progression of LVH individually. The present study explored the combined treatment of H2S and NO in the progression of LVH, and demonstrated that the response is due to H2S, NO or formation of either new molecule in physiological, pathological, and pharmacological in vivo settings of LVH. Exogenous administration H2S+NO in LVH significantly reduced (all p < 0.05) systolic blood pressure (SBP) and mean arterial pressure (MAP), LV index, heart index and oxidative stress when compared to the LVH group. There was downregulation of CSE mRNA and eNOS in the heart, and exogenous administration of H2S+NO groups upregulated eNOS MRNA while CSE MRNA remained downregulated in the hearts of the LVH group. Similar trends were observed with concentrations of H2S and NO in the plasma and tissue. It can be concluded that combined treatment of LVH with H2S and NO significantly ameliorate the progression of LVH by attenuating systemic hemodynamic and physical indices, and by decreasing oxidative stress. Molecular expression data in the myocardium of LVH depicts that combined treatment upregulated eNOS/NO while it downregulated CSE/H2S pathways in in vivo settings, and it is always eNOS/NO pathways which play a major role.

Highlights

Received: 10 December 2021The family of endogenous gaseous mediators comprised of nitric oxide (NO), hydrogen sulphide (H2 S) and carbon monoxide (CO) [1]
We previously reported that L-arginine, a donor of NO, increases the H2 S concentration in normal animals, but this interaction was absent in the Left ventricular hypertrophy (LVH) disease model when treated with an NO donor [24]
We reported that enhanced expression of endothelial nitric oxide synthase in the myocardium ameliorates the progression of left ventricular hypertrophy in L-arginine treated Wistar-Kyoto rats [4]

Summary

Introduction

Received: 10 December 2021The family of endogenous gaseous mediators comprised of nitric oxide (NO), hydrogen sulphide (H2 S) and carbon monoxide (CO) [1]. Endothelial nitric oxide synthase (eNOS) is constituted in left ventricular myocytes [3,4]. Literature reported that upregulation of eNOS in the myocardium arrests the progression of left ventricular hypertrophy (LVH) [4], and activation of eNOS in cardiomyocytes is a well-known antihypertrophic agent [5]. Therapeutic effects of NO in LVH are multifactorial, and lowering of systemic hemodynamics is one of the factors [4,7]. It can be deduced from the above literature that provision of the ENOS/NO pathway arrests the progression of LVH, while on the other side, deficiency of eNOS can develop sever cardiac hypertrophy [8]. It was interesting to know that supplementation of L-arginine, an NO donor, played an antihypertrophic role in the genetic model of hypertensive rats without lowering of blood pressure [11]; this same role is attributed with the lowering of Accepted: 8 January 2022

Results

Discussion

Conclusion