Up Regulation of cystathione γ lyase and Hydrogen Sulphide in the Myocardium Inhibits the Progression of Isoproterenol–Caffeine Induced Left Ventricular Hypertrophy in Wistar Kyoto Rats

Abstract

Hydrogen sulphide (H2S) is an emerging molecule in many cardiovascular complications but its role in left ventricular hypertrophy (LVH) is unknown. The present study explored the effect of exogenous H2S administration in the regression of LVH by modulating oxidative stress, arterial stiffness and expression of cystathione γ lyase (CSE) in the myocardium. Animals were divided into four groups: Control, LVH, Control-H2S and LVH-H2S. LVH was induced by administering isoprenaline (5mg/kg, every 72 hours, S/C) and caffeine in drinking water (62mg/L) for 2 weeks. Intraperitoneal NaHS, 56μM/kg/day for 5 weeks, was given as an H2S donor. Myocardial expression of Cystathione γ lyase (CSE) mRNA was quantified using real time polymerase chain reaction (qPCR).There was a 3 fold reduction in the expression of myocardial CSE mRNA in LVH but it was up regulated by 7 and 4 fold in the Control-H2S and LVH-H2S myocardium, respectively. Systolic blood pressure, mean arterial pressure, pulse wave velocity were reduced (all P<0.05) in LVH-H2S when compared to the LVH group. Heart, LV weight, myocardial thickness were reduced while LV internal diameter was increased (all P<0.05) in the LVH-H2S when compared to the LVH group. Exogenous administration of H2S in LVH increased superoxide dismutase, glutathione and total antioxidant capacity but significantly reduced (all P<0.05) plasma malanodialdehyde in the LVH-H2S compared to the LVH group. The renal cortical blood perfusion increased by 40% in LVH-H2S as compared to the LVH group. Exogenous administration of H2S suppressed the progression of LVH which was associated with an up regulation of myocardial CSE mRNA/ H2S and a reduction in pulse wave velocity with a blunting of systemic hemodynamic. This CSE/H2S pathway exhibits an antihypertrophic role by antagonizing the hypertrophic actions of angiotensin II(Ang II) and noradrenaline (NA) but attenuates oxidative stress and improves pulse wave velocity which helps to suppress LVH. Exogenous administration of H2S augmented the reduced renal cortical blood perfusion in the LVH state.

Cystathione gamma lyase/Hydrogen Sulphide Pathway Up Regulation Enhances the Responsiveness of α1A and α1B-Adrenoreceptors in the Kidney of Rats with Left Ventricular Hypertrophy

“…Increased SBP, MAP and LV index in response to model induction in present study is in line with our previous study on this model [ 52 ]. Exogenous administration of H 2 S significantly restored the manifestation of LVH pointing out antihypertrophic role of H 2 S which has also been recently reported [ 36 ]. The exogenous administration of NaHS in LVH rats increased the blunted renal cortical blood perfusion.…”

“…Molecular study was conducted as described previously [ 36 ]. Briefly the protocol consisted of the following steps; after cervical dislocation of the rat, kidney cortex was immediately preserved in RNAlater® Solution (Ambion, Life technologies, USA), while RNaseZap® (ambion, Life technologies, USA) was used to prevent any contamination.…”

Immunomodulatory, cytotoxicity, and antioxidant activities of roots of Ziziphus mauritiana

“…Increased MDA indicates the presence of free radicals and onset of diseases left ventricular hypertrophy. [ 20 ] These free radicals are culprit for the onset of many diseases where MDA is elevated locally and systemically. Antioxidants are responsible to counteract these free radicals and increase the antioxidant mechanisms of the body such as SOD and T-AOC.…”

Role of Nitric Oxide in the Cardiovascular and Renal Systems

“…Similarly, NO has been reported to play a renoprotective role in the chronic angiotensin-induced model of hypertension [ 103 ]. Ang II levels were found to be elevated in LVH [ 104 ], while administration of exogenous l -arginine inhibited the progression of LVH by increasing plasma and myocardium levels of NO [ 56 ]. It is known that Ang II levels are increased while NO levels are reduced in LVH, and LVH resulted in decreased responsiveness of α-adrenergic receptors to adrenergic agonists [ 90 , 105 ].…”