Mechanism of opioid-induced atrial natriuretic peptide release in conscious rats

To examine the role of atrial stretch and vasopressin in opiate-induced atrial natriuretic peptide (ANP) release, we studied the effects of a mu receptor agonist fentanyl on plasma immunoreactive ANP (IR-ANP) and hemodynamics (mean arterial pressure, heart rate and right atrial pressure) in the conscious, chronically cannulated Wistar, Long-Evans (LE) and vasopressin-deficient Brattleboro (DI) rats. Infusion of fentanyl (3 and 10 micrograms/kg i.v.) produced an immediate decrease in heart rate in conscious Wistar rats, whereas mean arterial pressure did not change significantly. Heart rate returned to control levels within 2 min of the injection, except after the largest dose of fentanyl when heart rate remained decreased for 5 min. Administration of 10 micrograms/kg of fentanyl caused a marked increase in right atrial pressure (3.9 +/- 0.3 mm Hg, n = 9, P less than .001) associated with 3.5-fold increase in the plasma IR-ANP concentration (168 +/- 17 pg/ml vs. 567 +/- 116 pg/ml, n = 9, P less than .01). In contrast, right atrial pressure decreased by 0.8 +/- 0.3 mm Hg (P less than .05) in response to infusion of 3 micrograms/kg of fentanyl with a slight increase (34%) in plasma IR-ANP. One microgram per kilogram i.v. of fentanyl had no effect on hemodynamic variables and plasma IR-ANP levels. Infusion of V1 antagonist (5 micrograms/kg/min for 25 min) did not affect basal or fentanyl-stimulated changes in hemodynamics or plasma IR-ANP concentration in Wistar rats. Infusion of fentanyl (3 and 10 micrograms/kg) in the LE and DI rats produced similar short-lasting heart rate reductions as seen in Wistar rats. Furthermore, injection of 10 micrograms/kg of fentanyl decreased blood pressure and increased plasma IR-ANP and right atrial pressure in both strains. The analysis of changes in plasma IR-ANP and right atrial pressure in response to fentanyl showed that for a given increase in right atrial pressure, a smaller amount of IR-ANP was released in the DI than in the LE rats. These results demonstrate that at higher fentanyl doses, the increased ANP release is mediated primarily by elevation of right atrial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)