Signaling cascade that mediates endothelial nitric oxide synthase activation induced by atrial natriuretic peptide.
Atrial natriuretic peptide (ANP) induces activation of nitric oxide-synthase (NOS).


OBJECTIVE
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 the 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. Calmodulin antagonist abolished NOS stimulation via ANP. Inhibition of the PLC, PKC or PI3 kinase/Akt pathway failed to alter NOS activation induced by ANP. ANP would activate eNOS in the 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 Ca(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.
Elesgaray
Rosana
R
Cátedra de Fisiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, IQUIMEFA-CONICET, Junín 956, piso 7, 1113 Capital Federal, Argentina.
Caniffi
Carolina
C
Ierace
Daniela Rodríguez
DR
Jaime
María Florencia Visintini
MF
Fellet
Andrea
A
Arranz
Cristina
C
Costa
María Angeles
MA
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology* / Q000502:physiology; D004727:Endothelium / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000201:enzymology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
D006146:Guanidines; C472610:atrial natriuretic peptide, rat; D009320:Atrial Natriuretic Factor; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester