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Título
Targeted genomic disruption of h-ras induces hypotension through a NO-cGMP-PKG pathway-dependent mechanism
Autor(es)
Assunto
Arterial pressure
cGMP-dependent protein kinase
Cyclic GMP
H-Ras protein
Nitric oxide
Soluble guanylyl cyclase
Fecha de publicación
2010-09
Editor
Lippincott Williams & Wilkins
Citación
Chamorro-Jorganes, A., Grande, M. T., Herranz, B., Jerkic, M., Griera, M., Gonzalez-Nuñez, M., Santos, E., Rodriguez-Puyol, D., Lopez-Novoa, J. M., & Rodriguez-Puyol, M. (2010). Targeted genomic disruption of h-ras induces hypotension through a NO-cGMP-PKG pathway-dependent mechanism. Hypertension (Dallas, Tex.: 1979), 56(3), 484-489. https://doi.org/10.1161/HYPERTENSIONAHA.110.152587
Resumen
[EN]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.
URI
ISSN
0194-911X
DOI
10.1161/HYPERTENSIONAHA.110.152587
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- GFCYR. Artículos [11]
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Artículo H-ras hypotension