Intermedin enhances sympathetic outflow via receptor-mediated cAMP/PKA signaling pathway in nucleus tractus solitarii of rats

Direct administration of intermedin (IMD) into the brain elicits cardiovascular effects different from the systemic administration. Nucleus tractus solitarii (NTS) is an important region for the cardiovascular regulation. The present study was designed to determine the effect of IMD on modulating the sympathetic outflow and its related molecular mechanism in the NTS. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anesthetized rats. Site-specific microinjection of IMD (20 pmol) bilaterally into the NTS significantly increased RSNA and MAP. IMD-evoked increases of RSNA and MAP were almost abolished by pretreatment with receptor antagonist ADM22-52, an adenylyl cyclase (AC) inhibitor 5Q22536, or a protein kinase A (PKA) inhibitor Rp-cAMP. However, pretreatment with another receptor antagonist calcitonin gene-related peptide (CGRP)8-37 did not suppress the increases of RSNA and MAP induced by IMD. Furthermore, IMD increased the cyclic adenosine monophosphate (cAMP) level, which was inhibited by ADM22-52 pretreatment in the NTS. These results suggest that IMD participates in the sympathetic nerve activity and central regulation of the cardiovascular system and a receptor-mediated cAMP/PKA signaling pathway is involved in IMD-induced effects in the NTS. (C) 2013 Elsevier Inc. All rights reserved.