The aims were to evaluate the role of cardiovascular nitric oxide (NO)-system in C-type natriuretic peptide (CNP) actions and to investigate receptor types and signaling pathways involved in this interaction. Wistar rats were infused with saline or CNP. Mean arterial pressure (MAP) and nitrites and nitrates (NOx) excretion were determined. NO synthase (NOS) activity and NOS expression (Western blot) were analyzed in atria, ventricle and aorta. CNP decreased MAP and increased NOx excretion. CNP estimulated NOS activity, inducing no changes on cardiac and vascular endothelial NOS expression. NOS activity induced by CNP was abolished by suramin and calmidazoliumand but it is not modified by anantin. CNP would interact with NPR-C receptor coupled via G proteins leading to the activation Ca2+-calmodulin dependent endothelial NOS, increasing NO production which would induce the reduction in cardiac myocyte contractility and ANP synthesis and secretion in right atria and the relaxation of vascular smooth muscle. (C) 2007 Elsevier Inc. All rights reserved.