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[Effects of adrenergic beta-receptor blocking drugs on brain catecholamine concentrations in spontaneously
Abstract:
To acquire data on the mechanism of central effects of adrenergic beta-blockers as antihypertensive agents, experiments were done on spontaneously hypertensive rats (SHR). Each group included 5 animals. Propranolol (5 mg/kg), pindolol (0.3 mg/kg), alprenolol (5 mg/kg) or bupranolol (5 mg/kg) were given subcutaneously to the respective groups, once daily for 7 days, while the control group were given no treatment. All the rats were sacrificed 12 hours after the last injection, and the concentrations of the following materials were measured: noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the brain; NA in the heart muscle; adrenaline and NA in the adrenal glands. As compared with the control group, all rats on the beta-blockers showed an increase in NA concentration in the brain. Both pindolol and alprenolol, which have an intrinsic sympathomimetic action (ISA), increased DA concentrations in the brain. Both propranolol and bupranolol, which have no ISA, either decreased DA concentrations or showed no effect. No marked change was seen in 5-HT concentration in the brain and of NA in the heart muscle. Catecholamine concentrations in the adrenal glands showed a tendency toward decrease. These results suggest that the mechanism of antihypertensive effects of beta-blockers may be due to depression of the peripheral sympathetic activity, as induced by the central inhibitory effects of beta-blockers.
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