CNP was originally isolated as a 22-amino-acid peptide from the porcine brain (Sudoh et al. 1990). The rat CNP precursor molecule, preproCNP, consists of 126 amino acid residues. It is a product of a gene that is distinct from the ANP or BNP genes and is highly conserved among species, with over 95 % homology among rat, human and porcine forms (for review see Nakao et al. 1992a). The biologically active CNP consists of 22 amino acids. The N-terminal-extended form, CNP-53, is the major form in porcine brain (Minamino et al. 1990). Immunoreactive CNP is found throughout the brain in the rat and humans, but outside the central nervous system little immunoreactive CNP is detected (Komatsu et al. 1991). However, in human breast tissue CNP immunostaining has been localized to vascular endothelial cells of small caliber arteries (Heublein et al. 1992). Using the RT-PCR method, transcripts of the CNP gene were detected in rat heart and kidney (Vollmar et al. 1993, Suzuki et al. 1993a), and CNP-like immunoreactivity has been found in human plasma using specific radioimmunoassay (Stingo et al. 1992b). CNP is synthesized and released from cultured endothelial cells (Suga et al. 1992). In cultured bovine endothelial cells both ANP and BNP stimulate CNP synthesis and secretion (Nazario et al. 1995). Other potent stimuli of CNP synthesis and secretion are cytokines and growth factors. TGF-β has been observed to induce an over 2-fold increase in CNP secretion in vascular endothelial cells (Suga et al. 1992). Moreover, CNP secretion is stimulated by TNF-α, IL-1, LPS, basic fibriblast growth factor (bFGF) and thrombin (Suga et al. 1993). Therefore, major components of the vascular wall, such as endothelial cells, platelets, and macrophages, secrete a number of factors that play a role in CNP synthesis and release. CNP acts as a specific agonist of NPR_B (Suga et al. 1992), which has been found in almost all tissues studied, including brain, kidney, aorta, liver, lung (Tallerico-Melnyk et al. 1992), aorta (Komatsu et al. 1992) and heart (Nunez et al. 1992). Activation of this receptor stimulates production of cGMP (Koller et al. 1991), which probaply mediates the biological effects.