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Is the antihypertensive effect of propranolol caused by an action within the central nervous system?

Propranolol in doses from 0.01 to 5 mg/kg x day was infused intracerebroventricularly (i.c.v.) in conscious unrestrained spontaneously hypertensive rats during 5 days by using Alzet osmotic minipumps. When given by this route, brain concentrations achieve values that are approximately 100-fold higher than those after s.c. infusion of equal doses, whereas plasma-levels are comparable. In this study we compared the dose needed to lower blood pressure upon i.c.v. infusion with the dose of 5 mg/kg x day dl-propranolol, which we reported earlier to induce a long lasting bradycardia and antihypertensive effect when infused s.c. Vehicle, 0.01 and 0.1 mg/kg x day of dl-propranolol, did not have any effect on mean arterial pressure or heart rate. Infusion (i.c.v.) of 1 mg/kg x day lowered heart rate during the first 4 days of the infusion. On the fifth day, this effect had disappeared. Also, during the first 2 days of the infusion a reduction of mean arterial pressure was observed, but thereafter pressure was at control levels. Infusion of 5 mg/kg x day of dl-propranolol reduced heart rate significantly from the first day of infusion throughout the whole infusion-period. On the other hand, mean arterial pressure was lowered with a delay of 1 day. It remained significantly below control values throughout the rest of the experimental period. d-Propranolol in a dose of 5 mg/kg x day i.c.v. did not have any effects. Since upon i.c.v. infusion the dose needed for a blood pressure lowering effect is the same as that needed for a s.c. infusion, in spite of 100-fold higher brain-levels, it is concluded that the antihypertensive effect of propranolol in spontaneously hypertensive rats is not caused by an action of the drug in the central nervous system.