Abstract:
:1. Cholestatic liver disease is associated with nitric oxide (NO) overproduction and bradycardia. Nitric oxide has a dual effect on sinoatrial node and its effects depend on its concentration. Nitric oxide can increase heart rate by activating hyperpolarization-activated pacemaker current (If) but, at high concentrations, it can potentially decrease heart rate by inhibition of L-type calcium current. In the present study, the responsiveness of isolated atria to CsCl (an inhibitor of the If current) and acetylcholine (ACh; which decreases L-type calcium current through a NO-dependent pathway) were evaluated in bile duct-ligated and sham-operated control rats. 2. Bile duct ligation induced a significant decrease in the negative chronotropic effect of CsCl (0.2-5 mmol/L), but increased the responsiveness of isolated atria to ACh (10-8 to 10-3 mol/L). These effects were restored after incubation of the atria in the presence of the NO synthase inhibitor NG-nitro-l-arginine methyl ester (0.1 mmol/L). 3. Anaesthetized bile duct-ligated rats showed bradycardia and the plasma levels of NO2-/NO3- were significantly higher in bile duct-ligated rats compared with sham-operated animals. 4. Different and opposite responses of atria of cholestatic rats to CsCl and ACh can be explained by NO overproduction in bile duct-ligated animals. A dual role of NO in the regulation of the sinoatrial node may be responsible for this opposite effect and may have a role in the pathophysiology of cholestasis-induced bradycardia.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Mani AR,Nahavandi A,Moosavi M,Safarinejad R,Dehpour ARdoi
10.1046/j.1440-1681.2002.03748.xkeywords:
subject
Has Abstractpub_date
2002-10-01 00:00:00pages
905-8issue
10eissn
0305-1870issn
1440-1681pii
3748journal_volume
29pub_type
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