Gender difference in rat aorta vasodilation after acute exposure to high glucose: Involvement of protein kinase C β and superoxide but not of Rho Kinase

Objectives: Several reports suggest that acute hyperglycemia affects male and female vascular beds differently. However, little is known about the interactions between hyperglycemia and gender in the vasculature. The objectives of our study were to investigate if there is a gender-based difference in the relaxation response of rat aorta after acute exposure to high glucose concentration, and the potential role of protein kinase C-beta (PKCβ), superoxide, and Rho kinase in the gender-specific effect of acute high glucose on the relaxation response. Methods: Endothelium-dependent dilator responses to acetylcholine (ACh, 10 to 10 M) were obtained before and after 3 h treatment with Krebs\u27 solution containing high glucose (46 mM) in aortic rings pre-contracted with phenylephrine (2 μM) taken from female and male Sprague-Dawley rats. Similar experiments were generated in the presence of 1 μM LY379196, a selective PKCβ inhibitor, 25 μM MnTMPyP, a superoxide dismutase mimetic, or 1 μM Fasudil, a Rho kinase inhibitor. Furthermore, protein expression of PKCβ isoforms was measured by Western blotting. Results: We demonstrated that a 3 h incubation with elevated level of glucose impairs ACh responses only in the female rat aortic rings. Inhibition of PKCβ or superoxide production but not Rho kinase prevents the high glucose-induced impairment of endothelium-dependent relaxation of female rat aorta. In addition, PKCβ2 expression is significantly higher in the female rat aorta than that in male rat aorta. Conclusion: These results suggest that the gender difference in the impairment of endothelium-dependent vasodilation after acute exposure to high glucose in rat aorta is possibly due to differences in PKCβ2 expression. © 2007 European Society of Cardiology. - 8 -