Beta-adrenoceptor blocking agents release catecholamines from rat adrenal medulla.

When small doses of pindolol and propranolol (0.1 mg/kg and 5 mg/kg, respectively) were administered intraperitoneally to conscious normotensive Kyoto Wistar rats, acute hypotension occurred. However, these hypotensive effects diminished when the doses were increased to 5 mg/kg and 20 mg/kg, respectively. Unilateral adrenalectomy had no effect on these hypotensive effects but they were suppressed by bilateral adrenalectomy. Subsequently, marked and lasting hypotensive effects (20-35 mm Hg) were observed. In urethane-anaesthetized rats, intravenous infusions of the blocking agents produced a rise in blood pressure and an increase in the content of epinephrine, norepinephrine and dopamine in adrenal venous blood. These hypertensive actions were not seen in adrenalectomized rats. When rats were given 6-hydroxydopamine (2 micrograms/microliters) bilaterally at the C4 level of the spinal cord 7 days before or 5,7-dihydroxytryptamine (2 micrograms/microliters, after desmethylimipramine, 25 mg/kg i.p.), the catecholamine content of adrenal venous blood and the catecholamine releasing actions of these blocking agents decreased, but were not completely abolished. These results suggest that the lack of hypotensive effects with higher doses of beta-adrenoceptor blocking agents may have been due partly to the direct release of catecholamines from the adrenal medulla and partly to central noradrenergic or serotonergic nerve action.