Targeted genomic disruption of h-ras induces hypotension through a NO-cGMP-PKG pathway-dependent mechanism.
Hypertension
; 56(3): 484-9, 2010 Sep.
Article
en En
| MEDLINE
| ID: mdl-20679183
The aim of the present experiments was to evaluate the differences in arterial pressure between H-Ras lacking mice and control mice and to analyze the mechanisms involved in the genesis of the differences. H-Ras lacking mice and mouse embryonic fibroblasts from these animals were used. Blood pressure was measured using 3 different methods: direct intraarterial measurement in anesthetized animals, tail-cuff sphygmomanometer, and radiotelemetry. H-Ras lacking mice showed lower blood pressure than control animals. Moreover, the aorta protein content of endothelial nitric oxide synthase, soluble guanylyl cyclase, and cyclic guanosine monophosphate-dependent protein kinase was higher in H-Ras knockout mice than in control animals. The activity of these enzymes was increased, because urinary nitrite excretion, sodium nitroprusside-stimulated vascular cyclic guanosine monophosphate synthesis, and phosphorylated vasoactive-stimulated phosphoprotein in aortic tissue increased in these animals. Furthermore, mouse embryonic fibroblasts from H-Ras lacking mice showed higher cyclic guanosine monophosphate-dependent protein kinase promoter activity than control cells. These results strongly support the upregulation of the nitric oxide-cyclic guanosine monophosphate pathway in H-Ras-deficient mice. Moreover, they suggest that H-Ras pathway could be considered as a therapeutic target for hypertension treatment.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Quinasas Dependientes de GMP Cíclico
/
GMP Cíclico
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Proteínas ras
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Hipotensión
/
Óxido Nítrico
Límite:
Animals
Idioma:
En
Revista:
Hypertension
Año:
2010
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
Estados Unidos