Local application of cyclic AMP in the rat brain: characterization of the cardiovascular response

Previous studies have demonstrated that central administration of dibutyryl cyclic AMP (DBcAMP) produces a dose-dependent rise in blood pressure accompanied by tachycardia. In an attempt to delineate brain sites that mediate these cardiovascular responses, DBcAMP was stereotaxically injected into local brain areas. Injections of 100 micrograms into the right lateral, third, and fourth ventricles produced pressor responses. Perfusion of the brain from the lateral ventricle to the cisterna magna with 15 micrograms/25 microliters per min induced a rise in blood pressure and significant bradycardia. The cyclic nucleotide was injected unilaterally in doses of 10, 25, and 50 micrograms into the posterior hypothalamic nucleus (PHN), anterior hypothalamic area (AHA), locus coeruleus (LC), and nucleus tractus solitarii (NTS). PHN injections induced tachycardia with minimal changes in blood pressure. Bradycardia and a depressor response were observed following injection of the 10 micrograms dose into the LC. Within the AHA, DBcAMP (10 micrograms) did not induce significant changes in cardiovascular function. Additionally, injections into the NTS initiated a biphasic depressor-pressor effect. Within these sites, cardiovascular responses to the 10 micrograms dose of DBcAMP paralleled those observed after adrenergic activation. These results strongly suggest that cyclic AMP functions as a second messenger within select central cardiovascular regulatory sites and plays an important role in cardiovascular regulation.