2026-09-15T04:52:07Zhttps://gredos.usal.es/oai/request

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

Targeted genomic disruption of h-ras induces hypotension through a NO-cGMP-PKG pathway-dependent mechanism 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 Arterial pressure cGMP-dependent protein kinase Cyclic GMP H-Ras protein Nitric oxide Soluble guanylyl cyclase [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. 2024-02-05T12:16:03Z 2024-02-05T12:16:03Z 2010-09 2099-12-31 info:eu-repo/semantics/article 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 eng 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 http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/embargoedAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional Lippincott Williams & Wilkins