The effect of opioids on rat plasma atrial natriuretic peptide.

The effect of multiple opioid receptor agonists on plasma immunoreactive atrial natriuretic factor (IR-ANF) was studied in conscious non-hydrated rats. We found that mu-opioid receptor agonists, given subcutaneously, increased plasma IR-ANF, while kappa-receptor agonists did not alter the plasma levels of IR-ANF. The mu-agonist fentanyl (0.05 mg/kg) caused a 10-fold increase in the concentration of IR-ANF, maximal levels being reached within 5-10 min. U 50,488-H and ethylketocyclazocine (EKC), both selective kappa-receptor ligands, were ineffective in this respect. The effect of fentanyl upon plasma IR-ANF was completely abolished by pretreatment with the narcotic antagonist naltrexone, proving opioid receptor specificity of the fentanyl effect. The quaternary antagonist N-methylnaltrexone (1 mg/kg) failed to block the fentanyl-induced increase of ANF, suggesting that opiates bring about their action on ANF via a central mechanism.