Site and mechanism of the centrally mediated hypotensive action of propranolol

Ventriculocisternal perfusion of propranolol (25 micrograms/kg/min for 30 min) throughout the entire brain ventricular system in anesthetized dogs decreased arterial pressure and increased cerebrospinal fluid (CSF) norepinephrine. Localized perfusion of propranolol into the fourth ventricle produced increased CSF norepinephrine levels and a hypotensive response comparable to that seen with whole-brain ventriculocisternal perfusion. In comparison, perfusion of propranolol through the forebrain (lateral-third) ventricles resulted in changes in CSF norepinephrine comparable to those observed with the administration of the drug into the fourth ventricle but resulted in a reduced hypotensive response. Increased CSF norepinephrine levels and a hypotensive response were also observed after peripheral i.v. infusion of propranolol (100 micrograms/kg/min for 45 min). Collectively, these results support the hypothesis that an interaction of propranolol at noradrenergic nerve terminals in the hindbrain area results in a hypotensive effect which may contribute to the antihypertensive action of the drug.