engleski

Vascular responses to acetylcholine- and hypoxia- induced dilation of diabetic ovariectomized rats

Objective: The aim of this study was to determine the effect of ovariectomy at 3rd week of age on vascular relaxation responses in healthy and diabetic female Sprague-Dawley (SD) rats. Materials and Methods: Twelve healthy, ovariectomized SD rats were divided in 4 groups: a) 12-weeks old control group (N=3) ; b) 16-weeks old control group (N=3) ; c) 12- weeks old (6 weeks DM) group (N=3) ; d) 16- weeks old (10 weeks of DM) group (N=3). Diabetes mellitus (DM) was induced by streptozocin 60mg/kg i.p. at 6th week of age, and duration of DM was 6 and 10 weeks, respectively. Prior to decapitation, rats were anesthetized with 75 mg/kg ketamine+2.5 mg/kg midazolam. Thoracic aortic rings were used to test acetylcholine (ACh) response (10-9-10-5 M) and response to reduced pO2 (bath gas mixture containing N2 95%, CO2 5%) after precontraction with noradrenaline (NA) for 5 minutes, in the absence/presence of the NOS inhibitor L-NAME or COX-1, 2 inhibitor indomethacin (INDO) in the tissue bath. Viability of rings at the end of the hypoxic protocol was tested with their ability to contract in 95% O2-5% CO2 bath solution. To test differences among groups Two- way ANOVA was used. Statistical significance was set at P<0.05 (SigmaPlot v11.2, Systat Software, Chicago, USA). Results: 6 weeks DM rats had significantly reduced ACh induced relaxation (AChIR) compared to respective age- control group (P<0.01 for 10-7M ACh concentration). L-NAME blocked AChIR in all 4 groups of rats (P<0.001 for 10-7-10-5 M ACh concentration), while INDO significantly reduced AChIR only in 10-weeks DM rats (P<0.001 for 10-7-10-5 M ACh) compared to respective age-control. Hypoxia induced significant relaxation (HIR) in all study groups. L-NAME blocked HIR in 12-weeks old control group, while INDO blocked HIR in 16-weeks old control group. In 16-weeks old DM group, both L-NAME and INDO significantly blocked HIR. Conclusion: These results demonstrate that: 1) vascular reactivity is impaired in diabetic rats ; 2) ACh–induced vasorelaxation is mediated by NO in control rats ; 3) metabolites of COX-1, 2 might play role in ACh- and hypoxia-induced relaxation in DM rats.

vascular function; acetylcholin; hypoxia; ovariectomy

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