Interaction of propranolol with central serotonergic neurons.
Central monoaminergic mechanisms are believed to be involved in cardiovascular regulation. The present study was designed to evaluate the involvement of central serotonergic pathways in the antihypertensive action of propranolol in pentobarbital anesthetized mongrel dogs. Ventriculocisternal perfusion of propranolol (25 ug/kg/min for 30 min) decreased serotonin turnover as indicated by a significant decrease in cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA). This effect was accompanied by a significant reduction in mean arterial pressure and heart rate. These results indicate that propranolol decreases central serotonergic activity and suggests a possible role for central serotonergic pathways in the antihypertensive action of propranolol. Several studies have indicated that central serotonergic pathways participate in the regulation of blood pressure. Brainstem regions including the nucleus tractus solitarius, the raphe nucleus and the anterior hypothalamic preoptic region are involved in cardiovascular control and contain a dense population of serotonergic neurons. A centrally-mediated hypotensive effect of propranolol has been demonstrated. Centrally administered propranolol increases cerebrospinal fluid (CSF) levels of norepinephrine and reduces blood pressure possibly due to decreased peripheral sympathetic nerve activity. Central serotonergic pathways may also be involved in the antihypertensive action of some beta-adrenoceptor antagonists. Destruction of central serotonergic neurons with 5,7-dihydroxytryptamine and desipramine abolished the antihypertensive effect of intracisternal propranolol in sinoaortic denervated dogs. Acute administrations of (-)-propranolol and (-)-pindolol decreased the synthesis rate of serotonin, while acute administration of salbutamol, a beta 2-adrenoceptor agonist, increased 5-HIAA levels in rat brain structures. The present study was designed to evaluate the involvement of central serotonergic pathways in the antihypertensive action of propranolol.
Jones
L F
LF
Cardiovascular Pharmacodynamics Laboratory, University of Georgia.
Tackett
R L
RL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D011433:Propranolol / Q000494:pharmacology*; D012016:Reference Values; D012701:Serotonin / Q000378:metabolism*
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D011433:Propranolol