Central administration of atrial peptide decreases sympathetic outflow in rats

Previously, we reported that intravenous (iv) administration of atrial natriuretic peptide (ANP) evokes a decrease in sympathetic outflow. This effect requires an afferent input from vagal C-fibers. Here, we examined the effect of intracerebroventricular (icv) administration of ANP on sympathetic outflow, as well as the potential role of central mechanisms in mediating the sympathoinhibitory effects evoked by systemic administration of the peptide. In anesthetized rats with arterial baroreceptors intact, injection of ANP (100-500 ng) into the third ventricle did not affect renal and least-splanchnic sympathetic nerve activities, heart rate, and mean arterial pressure. After sinoaortic denervation, however, icv injection of ANP (100 ng) decreased these variables by 8 +/- 1 and 9 +/- 2% of control nerve activity, 9 +/- 3 beats/min, and 13 +/- 2 mmHg, respectively (P less than 0.05). The inhibitory sympathetic and cardiovascular effects of icv ANP were dose dependent, with responses seen after doses too small to produce systemic effects (less than 100 ng). Vagal blockade did not abolish the effects evoked by icv ANP. In addition, iv administration of ANP did not alter reflex responses to graded electrical stimulation of afferent vagal C-fibers. Furthermore, central administration of an antiserum directed against rat ANP did not alter the inhibitory sympathetic responses evoked by iv administration of the peptide. Taken together, these results indicate that centrally administered ANP, like systemic ANP, decreases sympathetic outflow, heart rate, and blood pressure; however, the central and peripheral actions of the peptide can be distinguished and appear to be independent.