Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp ituitary adenylate cyclase-activating polypeptide (PACAP) is a regulatory peptide that was first isolated from the ovine hypothalamus. 1 PACAP exists in 2 amidated forms of either 38 and 27 residues, designated PACAP38 and PACAP27, respectively. 2 PACAP is a member of the vasoactive intestinal polypeptide (VIP)/secretin/ growth hormone releasing hormone family of peptides, and its amino acid sequence shows great similarity to VIP.PACAP and VIP share 3 kinds of receptors, namely PAC1-receptor (PAC1R), and the VPAC1 and VPAC2 receptors. The affinity of PAC1R with PACAP is 100-1,000 times higher than with VIP, indicating that PAC1R is a relatively selective receptor for PACAP. 3 PACAP is widely distributed in the brain and peripheral organs in mammals, and reportedly has diverse functions in the endocrine, nervous, gastrointestinal, immune, and cardiovascular systems. 4,5 PACAP and its receptors have also been identified in mammalian heart. 6-11 PACAP modulates the excitability of intracardiac neurons 6,12,13 and has positive inotropic, chronotropic, and dromotoropic effects on cardiomyocyte. 14-16 PACAP is also a potent vasodilator in various organs, including coronary and pulmonary arteries. PACAP and its receptors are expressed in the heart, but it is unclear whether PACAP exerts its protective effect on the myocardium in vivo. The aim of the present study was to investigate whether endogenous PACAP has a cardioprotective effect on Doxorubicin (Dox)-induced cardiomyopathy.