We have demonstrated previously that atrial natriuretic peptide (ANP) inhibits hypotension-induced reflex tachycardia via a parasympathetic mechanism. The present study further defines that parasympathetic mechanism. We tested the hypothesis that ANP, during vagus nerve stimulation, acts as a physiological antagonist to interfere with alpha 1-adrenoceptor modulation of efferent cardiac vagal action. Sprague Dawley rats were divided into five groups, each group receiving a different infusion. Infusates included one of vehicle (Ringer's solution; RS), an alpha 1-adrenoceptor agonist (phenylephrine; PE), a combination of agonist and either a known alpha 1-adrenoceptor antagonist (prazosin; PE+PRZ) or the putative physiologic antagonist, ANP (PE+ANP). The fifth group received all three drugs, PE+PRZ+ANP. Under Inactin anesthesia (100 mg/kg i.p.), efferent autonomic input to the heart was surgically interrupted. Animals were also adrenalectomized to limit the effects of circulating catecholamines. We then monitored each group for the change in heart rate (delta HR) in response to efferent vagus nerve stimulation at various frequencies (2 Hz, 5 Hz, 10 Hz). Infusion of PE significantly (P < 0.01 by ANOVA) attenuated the magnitude of delta HR when compared to the RS group. This attenuation of vagally-induced bradycardia was eliminated by the addition of the alpha 1-adrenoceptor antagonist, prazosin (PE+PRZ group). The PE+ANP group responded with results similar to those of the PE+PRZ group. There was no difference between delta HR responses of the PE+PRZ+ANP group and the PE+PRZ group.(ABSTRACT TRUNCATED AT 250 WORDS)