THE INTERACTION BETWEEN ATRIAL-NATRIURETIC-PEPTIDE AND CARDIAC PARASYMPATHETIC FUNCTION

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 alpha1-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 alpha1-adrenoceptor agonist (phenylephrine; PE), a combination of agonist and either a known alpha1-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 (DELTAHR) 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 DELTAHR when compared to the RS group. This attenuation of vagally-induced bradycardia was eliminated by the addition of the alpha1-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 DELTAHR responses of the PE + PRZ + ANP group and the PE + PRZ group. The results show that, in a setting of experimentally manipulated autonomic input to the heart, ANP produces a response to vagus nerve stimulation that is equivalent to that seen with the alpha1-adrenoceptor antagonist prazosin. Furthermore, in the presence of prazosin, ANP had no additional chronotropic effects. These results are consistent with our hypothesis that ANP influences parasympathetic control of heart rate by modifying the consequences of alpha1-adrenergic receptor activation.