2026-08-25T21:35:49Zhttps://gredos.usal.es/oai/request

oai:gredos.usal.es:10366/1553412026-01-21T11:18:05Zcom_10366_154280com_10366_4512com_10366_3823col_10366_154281

Chamorro-Jorganes, Aranzazu Grande, Maria Teresa Herranz, Beatriz Jerkic, Mirjana Griera, Mercedes González Núñez, María Santos de Dios, Eugenio Miguel Rodríguez-Puyol, Diego López-Novoa, José M. Rodriguez-Puyol, Manuel 2024-02-05T12:16:03Z 2024-02-05T12:16:03Z 2010-09 2099-12-31 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 0194-911X http://hdl.handle.net/10366/155341 10.1161/HYPERTENSIONAHA.110.152587 20679183 1524-4563 [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. Ministerio de Educación y Ciencia; Ministerio de Sanidad; Junta de Castilla León eng Lippincott Williams & Wilkins Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/embargoedAccess Arterial pressure cGMP-dependent protein kinase Cyclic GMP H-Ras protein Nitric oxide Soluble guanylyl cyclase Aorta Fibroblasts Cells Nitric Oxide Statistics Blood Pressure Cyclic GMP Hypotension Cyclic GMP-Dependent Protein Kinases Guanylate Cyclase Phosphorylation Nitric Oxide Synthase Type III Immunohistochemistry Animals Signal Transduction Up-Regulation ras Proteins Mice inmunohistoquímica fibroblastos hipotensión transducción de señales ratones óxido nítrico guanilato ciclasa regulación positiva proteínas ras proteínas cinasas dependientes de GMP cíclico presión sanguínea aorta células animales estadísticas GMP cíclico óxido nítrico sintasa de tipo III fosforilación Targeted genomic disruption of h-ras induces hypotension through a NO-cGMP-PKG pathway-dependent mechanism info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion https://doi.org/10.1161/HYPERTENSIONAHA.110.152587 SAF2004-07845-C02 SAF2004-07845-C02-01 SAF2007-6389 SAF 2007-623471 PI070695 RD6/0016 SA001/C05 SA029/A05 GR100 Hypertension (Dallas, Tex. : 1979) 56 3 484 489