Journal article
Sex-dependent differences in Rho activation contribute to contractile dysfunction in type 2 diabetic mice
American journal of physiology. Heart and circulatory physiology, Vol.297(4), pp.H1469-H1477
10/2009
DOI: 10.1152/ajpheart.00407.2009
PMID: 19666843
Abstract
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+/+ Leprdb/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 ∼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.
Details
- Title: Subtitle
- Sex-dependent differences in Rho activation contribute to contractile dysfunction in type 2 diabetic mice
- Creators
- Daniel W Nuno - the Departments of 2Internal Medicine andJeremy S Harrod - Department of Veterans Affairs Iowa City Health Care System andKathryn G Lamping - Department of Veterans Affairs Iowa City Health Care System and, the Departments of 2Internal Medicine and, Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.297(4), pp.H1469-H1477
- DOI
- 10.1152/ajpheart.00407.2009
- PMID
- 19666843
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Language
- English
- Date published
- 10/2009
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984094719502771
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