SEXUAL DIMORPHISM IN AORTIC ENDOTHELIALFUNCTION OF STZ-INDUCED DIABETIC AND ZDF RATS:POSSIBLE OF INVOLVEMENT OF ALTERED NITRIC OXIDEPRODUCTION

Background: Little is known about the interaction between diabetesand sex in vasculature. This study was designed to investigate whetherthere were sex differences in aortic endothelium-dependent vasodila-tion (EDV) in streptozotocin (STZ)-induced diabetic and Zuckerdiabetic fatty (ZDF) rats, and the potential role of nitric oxide indiabetes-induced vascular dysfunction in male and female rats.Methods: Diabetes was induced in male and female Sprague Dawley(SD) rats, 8 weeks after a single i.v. injection of STZ (60 mg/kg).Additionally, 16-week old male and female ZDF rats (fa/fa) and theirlean (fa/-) were used. EDV to acetylcholine (ACh, 10-8–10-5M) wasmeasured in rat aortic rings pre-contracted with phenylephrine (PE,2 lM). NO production was determined indirectly by generating con-centration response curves to PE (10-8–10-5M) in aortic rings beforeand after pretreatment with L-NAME (200 lM), a nitric oxide syn-thase (NOS) inhibitor. Furthermore, the levels of NADPH oxidase(Nox, a potent source of superoxide), eNOS and iNOS mRNA expres-sion in aorta were determined using real-time RT-PCR. Results: STZ-induced and ZDF diabetes impaired EDV to ACh onlyin aorta taken from females. Incubation of aortic rings with L-NAMEpotentiated PE responses in all groups, but aortae from control femalesshowed a greater potentiation of the PE response compared with othergroups in STZ study. STZ-diabetes reduced the extent of PE potentia-tion after L-NAME and the aortic eNOS mRNA expression in femalesto the same levels as seen in males. Unlike STZ diabetic females, ZDFdiabetic females were characterized by a greater potentiation of the PEresponses after L-NAME and a higher aortic eNOS mRNA expressioncompared with male groups. Finally, the levels of aortic Nox1 andiNOS mRNA expression were substantially enhanced in diabetes,regardless of the type of disease. Conclusions: These data suggest that an alteration in NO productionmay partially contribute to the predisposition of the female rat aorta toinjury in diabetes