title: Heme oxygenase-1 gene expression increases vascular relaxation and decreases inducible nitric oxide synthase in diabetic rats.
abstract: Hyperglycemia represents the main cause of complication of diabetes mellitus and oxidative stress, resulting from increased generation of reactive oxygen species (ROS), and plays a crucial role in their pathogenesis. Impairment of vascular responses in diabetic rats, as a result of an increase in superoxide (O2-), formation is a major complication in diabetes. Since heme oxygenase (HO) expression regulates the level of ROS by increasing antioxidant, such as glutathione and bilirubin, we investigated whether upregulation of HO-1 modulates the levels of iNOS and eNOS and altered vascular responses to phenylephrine (PE) and acetylcholine (Ach) in aorta and femoral arteries of diabetic (streptozotocin (STZ)-induced) rats. Our results showed that iNOS expression was increased, but HO activity was reduced, in diabetic compared to nondiabetic rats (p<0.05). Upregulation of HO-1 expression by cobalt protoporphyrin (CoPP), an inducer of HO-1 protein and activity, conferred an increase in eNOS and differentially decreased iNOS protein levels (p<0.05). Isolated aortic and femoral arteries obtained from diabetic rats exhibited contraction to PE and relaxation to Ach, which were markedly increased and decreased, respectively. However, HO-1 induction in diabetic rats normalized relaxation compared to controls. Therefore, overexpression of HO-1 may mediate an increase in eNOS and a decrease in iNOS, potentially contributing to restoration of vascular responses in diabetic rats.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ahmad
authors.forename: S
authors.initials: S
authors.lastname: Turkseven
authors.forename: C J
authors.initials: CJ
authors.lastname: Mingone
authors.forename: S A
authors.initials: SA
authors.lastname: Gupte
authors.forename: M S
authors.initials: MS
authors.lastname: Wolin
authors.forename: N G
authors.initials: NG
authors.lastname: Abraham
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D003925:Diabetic Angiopathies / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology*; D042783:Endothelial Cells / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000494:pharmacology; D014664:Vasodilation / Q000235:genetics*
chemical_list: D010656:Phenylephrine; D013311:Streptozocin; D052247:Nitric Oxide Synthase Type II; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D000109:Acetylcholine