title: Sexual dimorphism in rat aortic endothelial function of streptozotocin-induced diabetes: possible involvement of superoxide and nitric oxide production.
abstract: Little is known of the interactions between diabetes and sex hormones on vascular function. The objectives of this study were to investigate whether there were sex differences in rat aortic endothelial function one week after the induction of streptozotocin (STZ)-diabetes, and to examine the potential roles of superoxide and nitric oxide (NO) in this sex-specific effect. Endothelium-dependent vasodilatation to acetylcholine (ACh) was measured in rat aortic rings before and after treatment with MnTMPyP (25µM), a superoxide dismutase. Contractile responses to phenylephrine (PE) were generated before and after treatment with l-NAME (200μM), a nitric oxide synthase (NOS) inhibitor. The mRNA expression of NADPH oxidase (Nox) and endothelial nitric oxide synthase (eNOS) were also determined. We demonstrated that (1) STZ-diabetes impaired endothelium-dependent vasodilatation to ACh to a greater extent in female than male aortae, (2) inhibition of superoxide enhanced sensitivity to ACh only in diabetic females, and (3) Nox1 and Nox4 mRNA expression were significantly elevated only in aortic tissue of diabetic females. Furthermore, incubation of aortic rings with l-NAME potentiated PE responses in all groups, but aortae from control females showed a greater potentiation of the PE response after NOS inhibition compared with others. STZ-diabetes reduced the extent of PE potentiation after l-NAME and the aortic eNOS mRNA expression in females to the same levels as seen in males. These data suggest that a decrease in NO, resulting from either decreased eNOS or elevated superoxide, may partially contribute to the predisposition of the female aorta to injury early in diabetes.
authors.affiliation: Department of Physiology & Pharmacology, Thomas J. Long School of Pharmacy & Health Sciences, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Physiology & Pharmacology, Thomas J. Long School of Pharmacy & Health Sciences, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA 94115, USA.
authors.forename: Leigh
authors.initials: L
authors.lastname: Anderson
authors.affiliation: Department of Physiology & Pharmacology, Thomas J. Long School of Pharmacy & Health Sciences, University of the Pacific, 3601 Pacific Avenue, Stockton, CA 95211, USA. Electronic address: rrahimian@pacific.edu.
authors.forename: Roshanak
authors.initials: R
authors.lastname: Rahimian
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D019255:NADPH Oxidases / Q000235:genetics; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013481:Superoxides / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D008665:Metalloporphyrins; C502230:Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; D014665:Vasodilator Agents; D013481:Superoxides; D010656:Phenylephrine; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019255:NADPH Oxidases; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester
keywords: Diabetes; Endothelial dysfunction; Nitric oxide; Sex difference; Superoxide