Signaling cascade that mediates endothelial nitric oxide synthase activation induced by atrial natriuretic peptide

ELESGARAY R.; CANIFFI C.; RODRIGUEZ IERACE D; VISINTINI F; FELLET A.; ARRANZ C; COSTA A.

REGULATORY PEPTIDES

Elsevier

Lugar: Holanda; Año: 2008 vol. 151 p. 130 - 134

0167-0115

Atrial natriuretic peptide (ANP) induces activation of nitric oxide-synthase (NOS). Aim: to identify the isoform of NOS involved in ANP effects, to study whether ANP modifies NOS expression and to investigate the signaling pathways and receptors involved in NOS stimulation. NOS activation induced by ANP would be mediated by endothelial NOS (eNOS) since neuronal or inducible NOS inhibition did not alter ANP effect. The peptide induced no changes in eNOS protein expression. NOS activity stimulated by ANP, in kidney, aorta and left ventricle, was partially abolished by the NPR-A/B antagonist, as well as PKG inhibition, but no difference in atria was observed. 8-Br-cGMP partially mimicked the effect of ANP on NOS in all tissues. NOS stimulation by ANP in atria disappeared when G protein was inhibited, but this effect was partial in the other tissues. Inhibition of the PLC, PKC or PI3 kinase/Akt pathway failed to alter NOS activation induced by ANP. ANP would activate eNOS in aorta, heart and kidney without modifying the expression of the enzyme. ANP would interact with NPR-C coupled via G proteins leading to the activation of Ca2+-calmodulin dependent NOS in atria; while in ventricle, aorta and kidney, ANP could also interact with NPR-A/B, increasing cGMP, which in turns activates PKG to stimulate eNOS. Key words: heart, kidney, aorta artery, NPR-C, NPR-A, cGMP. interact with NPR-A/B, increasing cGMP, which in turns activates PKG to stimulate eNOS. Key words: heart, kidney, aorta artery, NPR-C, NPR-A, cGMP. interact with NPR-A/B, increasing cGMP, which in turns activates PKG to stimulate eNOS. Key words: heart, kidney, aorta artery, NPR-C, NPR-A, cGMP. interact with NPR-A/B, increasing cGMP, which in turns activates PKG to stimulate eNOS. Key words: heart, kidney, aorta artery, NPR-C, NPR-A, cGMP. 2+-calmodulin dependent NOS in atria; while in ventricle, aorta and kidney, ANP could also interact with NPR-A/B, increasing cGMP, which in turns activates PKG to stimulate eNOS. Key words: heart, kidney, aorta artery, NPR-C, NPR-A, cGMP.