The role of rho kinase in sex-dependent vascular dysfunction in type 1 diabetes.
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.
Nuno
Daniel W
DW
The Department of Veterans Affairs Iowa City Health Care System, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, IA 52246, USA.
Lamping
Kathryn G
KG
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000209:etiology*; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012727:Sex Characteristics; D013311:Streptozocin; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D054460:rho-Associated Kinases / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology
D013311:Streptozocin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; C049347:fasudil