EDN1 and Hyperglycemia: Furthermore, hyperglycaemia is also known to activate protein kinase C (PKC), which decreases eNOS activity, leading to reduced NO and increased ET-1 production.24 In the setting of ED, ETB receptor-mediated vasodilatory effects of ET-1 are blunted (refer to Table 1) and therefore the vasoconstrictory state predominates.26 PKC also enhances the expression of adhesion molecules such as ICAM, VCAM and E-selectin,24 which is associated with endothelial cell activation.