Fundamental & clinical pharmacology
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Fundam Clin Pharmacol · Oct 2006
Involvement of endogenous opioid peptides and nitric oxide in the blunted chronotropic and inotropic responses to beta-adrenergic stimulation in cirrhotic rats.
It is well known that chronotropic and inotropic responses to beta-adrenergic stimulation are impaired in cirrhosis, but the exact reason is not clear. Considering the inhibitory effect of endogenous opioid peptides and nitric oxide (NO) on beta-adrenergic pathway, we examined their roles in hyporesponsiveness of isolated atria and papillary muscles to isoproterenol stimulation in cirrhotic rats. Cirrhosis was induced by chronic bile duct ligation. ⋯ Concurrent administration of naltrexone and L-NAME also restored to normal the basal abnormalities and the blunted responses to isoproterenol in cirrhotic rats, and did not show any antagonistic effect. Based on these findings, both the endogenous opioid peptides and NO may be involved in the attenuated chronotropic and inotropic responses to beta-adrenergic stimulation in cirrhosis. It seems that the iNOS activity results in NO-induced hyporesponsiveness to beta-adrenergic stimulation in cirrhosis.