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Sex differences and sex-hormones role in aortic reactivity to acethylcholine in Sprague-Dawley rats with and without streptozotocin induced diabetes mellitus

Introduction: The effect of sex hormones on vascular reactivity is considered one of the underlying factors contributing to gender differences in cardiovascular functions and diseases. Several reports suggest that hyperglycemia affects male and female vascular beds differently. However, little is known about the interactions between hyperglycemia and sex differences in the vasculature. Present study aimed to investigate if there is a sex- based difference in the aortic relaxation response to acethylcholine (ACh) in male and female (non-ovariectomized /ovariectomized (OVX)) Sprague-Dawley rats with and without streptozotocin induced diabetes mellitus (DM). Methods: Total of 31 rats were divided in 2 groups of male (healthy controls (CTRL, n=5) and streptozotocin-induced diabetic rats (DM, n=5) and 4 groups of female Sprague-Dawley rats: non-ovariectomized healthy rats (non-ovx CTRL, n=5), non-ovariectomized diabetic rats (non-ovx DM, n=5), ovariectomized healthy rats (ovx-CTRL, n=6) and ovariectomized DM rats (ovx DM, n=5). Bilateral ovariectomy was performed under anesthesia (75 mg/kg ketamine + 2.5 mg/kg midazolam i.p.) at the 5th week of age. DM was induced by streptozotocin (60mg/kg i.p.) at the 6th week of age, in duration of 6 weeks before experiments. ACh induced relaxation (AChIR) (10-9-10-5M) was tested in thoracic aortic rings after 5’ noradrenaline (NA) precontraction. Results: Female controls and non-ovariectomized diabetic rats have better AChIR compared to their male match (male control and male DM respectively). AChIR was similar between DM and control group of rats at both sexes, as well as between male controls and OVX rats. However, AChIR was significantly impaired in OVX DM group compared to OVX CONTROLS. Discussion: These results suggest that aortic function in female ovariectomized rats exhibits a more prominent impairment compared to non-OVX rats. There is a basic sex difference in relaxation responses. Conclusion: Study suggests important protective role of female sex hormones in vascular reactivity. Acknowledgments: All experimental procedures conformed to the European Guidelines for the Care and Use of Laboratory Animals (directive 86/609) and were approved by the local Ethical Committee #2158/61-07-14-124.

sex differences; diabetes mellitus; Sprague-Dawley rats

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