Differential role of S-nitrosylation and the NO-cGMP-PKG pathway in cardiac contractility

Simple item page
dc.contributor.authorGonzalez, Daniel R.
dc.contributor.authorFernandez, Ignacio C.
dc.contributor.authorOrdenes, Pablo P.
dc.contributor.authorTreuer, Adriana V.
dc.contributor.authorEller, Gisela
dc.contributor.authorBoric, Mauricio P.
dc.date.accessioned2025-01-21T01:05:07Z
dc.date.available2025-01-21T01:05:07Z
dc.date.issued2008
dc.description.abstractThe role of nitric oxide (NO) in cardiac contractility is complex and controversial. Several NO donors have been reported to cause positive or negative inotropism. NO can bind to guanylate cyclase, increasing cGMP production and activating PKG. NO may also directly S-nitrosylate cysteine residues of specific proteins. We used the isolated rat heart preparation to test the hypothesis that the differential inotropic effects depend on the degree of NO production and the signaling recruited. SNAP (S-nitroso-N-acetylpenicillamine), a NO donor, increased contractility at 0.1, 1 and 10 M. This effect was independent of phospholamban phosphorylation, was not affected by PKA inhibition with H-89 (N-[2((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide), but it was abolished by the radical scavenger Tempol (4-hydroxy-[2,2,4,4]-tetramethyl-piperidine-1-oxyl). However, at 100 mu M SNAP reduced contractility, effect reversed to positive inotropism by guanylyl cyclase blockade with ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), and abolished by PKG inhibition with KT5823, but not affected by Tempol. SNAP increased tissue cGMP at 100 M, but not at lower concentrations. Consistently, a cGMP analog also reduced cardiac contractility. Finally, SNAP at 1 mu M increased the level of S-nitrosylation of various cardiac proteins, including the ryanodine receptor. This study demonstrates the biphasic role for NO in cardiac contractility in a given preparation; furthermore, the differential effect is clearly ascribed to the signaling pathways involved. We conclude that although NO is highly diffusible, its output determines the fate of the messenger: low NO concentrations activate redox processes (S-nitrosylation), increasing con-tractility;while the cGMP-PKG pathway is activated at high NO concentrations, reducing contractility. (c) 2007 Elsevier Inc. All rights reserved.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.niox.2007.09.086
dc.identifier.eissn1089-8611
dc.identifier.issn1089-8603
dc.identifier.urihttps://doi.org/10.1016/j.niox.2007.09.086
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/95822
dc.identifier.wosidWOS:000254911500003
dc.issue.numero3
dc.language.isoen
dc.pagina.final167
dc.pagina.inicio157
dc.revistaNitric oxide-biology and chemistry
dc.rightsacceso restringido
dc.subjectnitric oxide
dc.subjectnitric oxide synthase
dc.subjectNOS
dc.subjectrat heart
dc.subjectlangendorff
dc.subjecttempol
dc.subjectSNAP
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleDifferential role of S-nitrosylation and the NO-cGMP-PKG pathway in cardiac contractility
dc.typeartículo
dc.volumen18
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
Files
Collections
Artículos de revistas