C-type natriuretic peptide has a negative inotropic effect on cardiac myocytes

C-type natriuretic peptide (CNP) has vasodilatory and antimitogenic actions , but its role in the control of cardiac function is unclear. We studied th e effect of CNP on cultured, beating neonatal rat cardiac myocytes. CNP cau sed a significant reduction in the amplitude of contraction and a significa nt accumulation of intracellular cyclic GMP. The effect of a membrane perme able cyclic GMP on cell contraction was similar to that of CNP. CNP caused no change in Ca2+ transients. Blockade of natriuretic peptide receptors abo lished the effects of CNP on contraction and accumulation of intracellular cyclic GMP. Blockade of cyclic GMP-dependent protein kinase abolished the e ffect of CNP on myocyte contraction We conclude that CNP has a negative ino tropic effect on neonatal rat cardiac myocytes. The effect of CNP is mediat ed via natriuretic peptide receptor(s) causing elevation of intracellular c yclic GMP which possibly activates protein kinase and causes attenuation of myofilament sensitivity to Ca2+. (C) 2001 Elsevier Science B.V. All rights reserved.