Document Detail


Targeted genomic disruption of h-ras induces hypotension through a NO-cGMP-PKG pathway-dependent mechanism.
MedLine Citation:
PMID:  20679183     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Aranzazu Chamorro-Jorganes; Maria Teresa Grande; Beatriz Herranz; Mirjana Jerkic; Mercedes Griera; Maria Gonzalez-Nuñez; Eugenio Santos; Diego Rodriguez-Puyol; Jose Miguel Lopez-Novoa; Manuel Rodriguez-Puyol
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-02
Journal Detail:
Title:  Hypertension     Volume:  56     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-19     Completed Date:  2010-09-13     Revised Date:  2010-09-23    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  484-9     Citation Subset:  IM    
Affiliation:
Department of Physiology, Universidad de Alcala, Alcala de Henares, Spain. aranzazu.chamorro@nyumc.org
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta / metabolism
Blood Pressure / physiology
Blotting, Northern
Blotting, Western
Cells, Cultured
Cyclic GMP / genetics,  metabolism*
Cyclic GMP-Dependent Protein Kinases / genetics,  metabolism*
Fibroblasts / cytology,  metabolism
Guanylate Cyclase / genetics,  metabolism
Hypotension / genetics,  metabolism*
Immunohistochemistry
Mice
Mice, Knockout
Nitric Oxide / genetics,  metabolism*
Nitric Oxide Synthase Type III / genetics,  metabolism
Phosphorylation
Receptors, Cytoplasmic and Nuclear / genetics,  metabolism
Signal Transduction / physiology
Statistics, Nonparametric
Up-Regulation / physiology
ras Proteins / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Receptors, Cytoplasmic and Nuclear; 10102-43-9/Nitric Oxide; 7665-99-8/Cyclic GMP; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 2.7.11.12/Cyclic GMP-Dependent Protein Kinases; EC 3.6.5.2/ras Proteins; EC 4.6.1.2/Guanylate Cyclase; EC 4.6.1.2/soluble guanylyl cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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