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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-9-25
pubmed:abstractText
The objective of this study was to determine if mechanisms involved in vascular dysfunction in type 2 diabetes differ with sex. Vascular reactivity, expression, and activation of rhoA and rho kinase were measured in aorta from male and female nondiabetic C57BLKS/J and diabetic BKS.Cg-m(+/+) Lepr(db)/J (db/db) mice, a model of type 2 diabetes. Relaxation to acetylcholine and nitroprusside was similar in aorta from nondiabetic male and female mice. Relaxation to acetylcholine was reduced approximately 50% in both male and female diabetic mice. Although inhibition of rho kinase with H-1152 increased relaxation to acetylcholine and nitroprusside in nondiabetic males, it had no effect on the response in either nondiabetic or diabetic females or diabetic males. Contraction to serotonin was increased similarly in male and female diabetic mice compared with nondiabetic mice and was reduced following inhibition of rho kinase with either fasudil or H-1152. Activation of rhoA and its downstream effector, rho kinase, was greater in aorta from diabetic males compared with nondiabetic males. In contrast, there were no differences in vascular activation of rhoA or rho kinase in diabetic females. The increased activity of rhoA and rho kinase in diabetic mice was not due to a change in protein expression of rhoA or rho kinase (ROCK1 and ROCK2) in vessels from either males or females. Although contractile dysfunction in vessels occurs in both male and female diabetic mice, the dysfunction in diabetic males is dependent upon activation of rhoA and rho kinase. Alternative mechanisms affecting rho kinase activation may be involved in females.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1522-1539
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
297
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H1469-77
pubmed:meshHeading
pubmed-meshheading:19666843-Animals, pubmed-meshheading:19666843-Aorta, pubmed-meshheading:19666843-Aortic Diseases, pubmed-meshheading:19666843-Diabetes Mellitus, Type 2, pubmed-meshheading:19666843-Diabetic Angiopathies, pubmed-meshheading:19666843-Disease Models, Animal, pubmed-meshheading:19666843-Dose-Response Relationship, Drug, pubmed-meshheading:19666843-Enzyme Activation, pubmed-meshheading:19666843-Female, pubmed-meshheading:19666843-Male, pubmed-meshheading:19666843-Mice, pubmed-meshheading:19666843-Mice, Inbred C57BL, pubmed-meshheading:19666843-Nitric Oxide, pubmed-meshheading:19666843-Protein Kinase Inhibitors, pubmed-meshheading:19666843-Serotonin, pubmed-meshheading:19666843-Sex Factors, pubmed-meshheading:19666843-Vasodilation, pubmed-meshheading:19666843-Vasodilator Agents, pubmed-meshheading:19666843-rho GTP-Binding Proteins, pubmed-meshheading:19666843-rho-Associated Kinases
pubmed:year
2009
pubmed:articleTitle
Sex-dependent differences in Rho activation contribute to contractile dysfunction in type 2 diabetic mice.
pubmed:affiliation
Department of Veterans Affairs Iowa City Health Care System, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't