Effects of (±)-sotalol, (±)-propranolol, and (−)-propranolol on norepinephrine release upon hepatic nerve stimulation in the dog liver in vivo

Abstract

The study was carried out to determine whether the diminished release of norepinephrine (NE) upon sympathetic activation in the presence of sotalol can be attributed to the blockade of beta-adrenoceptors in the liver. NE release from the liver was measured in hepatic venous blood collected during direct hepatic nerve stimulation in anesthetized dogs. The mean basal NE concentration in hepatic venous and aortic blood was 0.046 +/- 0.003 and 0.244 +/- 0.041 ng/mL, respectively. NE release increased significantly as stimulation frequency increased, while aortic NE concentration remained unchanged. The increasing response of NE release upon stimulation in the vehicle control group remained stable during the whole experimental period. In dogs treated with sotalol (5 mg/kg, i.v.), NE release was reduced approximately by 30-43%, and the difference was statistically significant (P less than 0.01) at 8 Hz. (+/-)-Propranolol (2.5 mg/kg, i.v.) tended to diminish it, but the difference was not significant. (-)-Propranolol (0.1 mg/kg, i.v.) did not alter NE release at any frequency tested. The beta-blocking action of these drugs in the liver, as determined by the antagonism against the hepatic arterial vasodilating response to isoproterenol, was most effective with (+/-)-propranolol (100%), followed by (-)-propranolol (90%) and sotalol (70%). The results suggest that the inhibitory effect of sotalol on NE release may be related to a mechanism other than its beta-blocking action in the dog liver.