Gender difference of vascular functional changes in diabetic condition

[Speaker] Yasuhiro Takenouchi:1,2
[Co-author] Kazuhito Tsuboi:1, Kazuo Ohtake:2, Keizo Kasono:2, Yasuo Okamoto:1
1:Pharmacology, Kawasaki Medical School, Japan, 2:Physiology, Josai University, Japan

[Background] While cardiovascular disease events in the non-diabetic patients are more frequent in men than in women, it has been reported that the women with diabetes have a higher risk for cardiovascular diseases than men with diabetes. Thus, diabetes may induce a greater impairment of cardiovascular function in female. Despite such a reversal by sex difference in epidemiological studies, vascular functional change by gender remains unknown.

[Methods] To induce diabetes, male and female mice received a single injection of streptozotocin (STZ; 200 mg/kg) via the tail vein. The age-matched normal mice were injected with similar volume of saline. Aortic rings were then isolated from mice elapsed 8 weeks after treatment with STZ or saline. Each aortic ring was placed in a bath containing Krebs-Henseleit solution, and the response to vasoactive reagents was measured by force-displacement transducer. For the relaxation studies, after the prostaglandin F2α-induced contraction had reached plateau level, acetylcholine (ACh), clonidine, insulin, or sodium nitro prusside (SNP) were added in a cumulative manner. For the contraction studies, norepinephrine was applied in a cumulative manner.

[Results] In both male and female, ACh-induced relaxation (endothelium-dependent) of aortic rings was impaired in diabetic mice, compared to normal mice. The SNP-induced relaxation (endothelium-independent) was not altered by diabetes in either male or female mice. The norepinephrine-induced contraction was enhanced in diabetic female mice, but not in diabetic male mice, compared with corresponding normal mice. Interestingly, in the presence of N(G)-nitro-L-arginine, a NO synthase inhibitor, neither gender exhibited a significant diabetes-induced change in this contraction. Furthermore, the clonidine- and insulin-induced endothelium-dependent aortic relaxations were impaired by diabetes only in female.

[Conclusion] These results suggest that the difference of the reactivity to various vasoactive reagents is involved in the reversal by sex differences in the vulnerability to cardiovascular diseases in diabetic condition.

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