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Experimental Diabetes Research
Volume 2010 (2010), Article ID 176361, 11 pages
http://dx.doi.org/10.1155/2010/176361
Research Article

The Role of Rho Kinase in Sex-Dependent Vascular Dysfunction in Type 1 Diabetes

1The Department of Veterans Affairs Iowa City Health Care System, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, IA 52246, USA
2Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, IA 52242, USA
3Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, IA 52242, USA

Received 17 September 2009; Revised 1 December 2009; Accepted 14 January 2010

Academic Editor: Subrata K. Chakrabarti

Copyright © 2010 Daniel W. Nuno and Kathryn G. Lamping. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We hypothesized that rho/rho kinase plays a role in sex differences in vascular dysfunction of diabetics. Contractions to serotonin were greater in isolated aortic rings from nondiabetic males versus females and increased further in streptozotocin-induced diabetic males but not females. The increased contractions to serotonin in males were reduced by inhibitors of rho kinase (fasudil, Y27632 and H1152) despite no change in expression of rhoA or rho kinase. Contractions to U46619 were not altered by fasudil or Y27632 or the presence of diabetes. In contrast to acute effects of fasudil, chronic treatment with fasudil increased contractions to serotonin in aorta from both non-diabetic and diabetic males. In summary, serotonin-induced contractions were increased in aorta from diabetic males but not females. Although administration of rho kinase inhibitors acutely decreased contractions to serotonin, long-term treatment with fasudil increased contractions. Long-term fasudil treatment may increase compensatory mechanisms to enhance vasoconstrictions.