Endogenous
hydrogen sulfide is produced by
cystathionine-γ-
lyase and
cystathionine-β-synthase in a variety of tissues and has recently been implicated in the regulation of cardiac functions. Acceleration of the heart rate in response to
catecholamines is impaired in patients with
cirrhosis. The present study was aimed to examine the role of endogenous
hydrogen sulfide in the pathogenesis of chronotropic dysfunction in rats with
cirrhosis.
Cirrhosis was induced by surgical
ligation of bile duct in rats. There was no significant difference in atrial
cystathionine-γ-
lyase and
cystathionine-β-synthase
mRNA levels in control and cirrhotic rats as assessed by quantitative RT-PCR. Four weeks after bile duct
ligation or
sham surgery the atria were isolated and chronotropic responsiveness to
adrenergic stimulation was assessed using standard organ bath. Incubation of the atria with
propargylglycine (PAG, a
cystathionine-γ-
lyase inhibitor) and amino-oxyacetic
acid (AOAA, a
cystathionine-β-synthase inhibitor) was associated with a significant desensitization of chronotropic response to
adrenergic stimulation in controls rats. This indicates that endogenous
hydrogen sulfide might be involved in modulation of
adrenergic signaling in the atrium. Bile duct
ligation was associated with impaired chronotropic responsiveness to
adrenergic stimulation in comparison with
sham-operated rats. In contrast to control group, incubation of the atria with PAG and AOAA was able to partially improve the chronotropic responsiveness to
adrenergic stimulation in cirrhotic rats. Our data shows that local inhibition of endogenous
hydrogen sulfide in atria has opposite effect in cirrhotic versus control rats and may play a role in physiological modulation of
adrenergic signaling in the atrium.