Gender differences in aortic endothelial function of streptozotocin‐induced diabetic rats: possible involvement of protein kinase C beta and nitric oxide production

Abstract

Little is known of the interaction between diabetes and gender in the vasculature. The objective of this study was to investigate whether there are gender differences in rat aortic endothelial function in streptozotocin (STZ, 60mg/kg, iv)‐induced diabetes and the roles of protein kinase C beta (PKCβ) and nitric oxide (NO). Endothelium‐dependent vasodilatation (EDV) to acetylcholine (ACh; 10−8 to 10−5M) was measured in aortic rings precontracted with phenylephrine (PE; 2μM) before and after pretreatment with LY341684 (1μM), a selective PKCβ inhibitor. Constrictor response curves to PE (10−8 to 10−5M) were also generated before and after incubation with L‐NAME (200μM), an endothelial nitric oxide synthase inhibitor. STZ‐induced diabetes impaired aortic EDV to ACh only in females. Inhibition of PKCβ increased the sensitivity to ACh in both control and diabetic male rats. However, PKCβ inhibition enhanced the sensitivity to ACh only in aorta taken from diabetic female rats. Addition of L‐NAME resulted in a significant potentiation of the contractile responses to PE in all groups. However, aorta from control females had a greater maximal potentiation of the PE responses than others. These data suggest that the predisposition of female rat aorta to vascular injury in diabetes is possibly due to differences in enhanced PKCβ activation and decreased basal NO production (supported by NIH/NIDCR).