031P Queen Elizabeth II Conference Centre London
Pharmacology 2015

 

Upregulation of cystathione ϒ lyase in the myocardium inhibits the progression of isoproterenol – caffeine induced left ventricular hypertrophy in male Wistar kyoto rats

 

Hydrogen sulphide (H2S) is an emerging molecule involved in many cardiac and vascular diseases. Its role in left ventricular hypertrophy (LVH) was investigated using exogenously administered H2S and determining its impact on LVH regression by oxidative stress, arterial stiffness and myocardial expression of cystathione ϒ lyase (CSE) modulation. Four groups of male rats were studied with Animal Ethics Committee Universiti Sains Malaysia (AECUSM) approval and under Pentobarbitone Sodium 60mg/kg (i.p) where required: Control, LVH, Control-H2S and LVH-H2S (n= 6 each). NaHS water solution a donor of H2S was given at 56μM/kg intra-peritoneally for 5 weeks. LVH was induced using isoprenaline (5mg/kg, every 72 hours, S.C.) and caffeine (62mg/L) in drinking water for the last 2 weeks (1). Myocardial expression of CSE mRNA was quantified using real time polymerase chain reaction (PCR). There was a 3 fold reduction in CSE mRNA and increase in mean arterial pressure (MAP) in LVH compared to the Control group. Exogenous administration of H2S up-regulated CSE mRNA expression by 7 and 4 folds in Control-H2S and LVH-H2S groups respectively with a corresponding decrease in MAP. Noradrenaline, angiotensin II levels in the plasma and PWV reduced (all P<0.05) in LVH-H2S vs. LVH group. LV weight and myocardial thickness reduced while LV internal diameter increased (all P<0.05) in LVH-H2S vs LVH group (Table 1). Exogenous administration of H2S in LVH increased the superoxide dismutase, glutathione, total antioxidant capacity and showed a 40 % increase in renal cortical blood perfusion but reduced malanodialdehyde in LVH-H2S as compared to the LVH group (all P<0.05).

 

Table 1. Effects of H2S on different parameters. * P<0.05 vs. Control while # P<0.05 vs.LVH

Parameters Control LVH Control-H2S LVH-H2S
CSE mRNA (folds change) 1±0.0 0.3±0.05* 2.3±0.07*# 1.2±0.09*#
Angiotensin II (pg/ml) in plasma 304±4 460±3* 250±3*# 339±3*#
Noradrenaline (pg/ml) in plasma 153±3 438±4* 116±2 283±5*#
LV index (%) 0.16±0.004 0.24±0.002* 0.19±0.006*# 0.21±0.001*#
Thickness of myocardium (mm) 1.6±0.07 3.3±0.04* 1.8±0.05*# 2.4±0.05*#
LV diameter (mm) 5±0.02 3±0.04 4±0.02*# 5±0.05*#
MAP (mmHg) 119±1 142±5* 122±6# 122±3#
RCBP (bpu) 156±8 94±6* 144±3# 134±4#

 

Exogenous administration of H2S suppressed the progression of LVH by up-regulation of myocardial CSE expression and down regulation of oxidative stress which was associated with reduced blood pressure and increased renal haemodynamics.

(1). Flanagan ET et al. (2008). Exp Physiol 93:1058-1064.