There have been many reports demonstrating that
various isolated vascular preparations from diabetic animals
show reduced relaxation in response to the endotheliumdependent and endothelium-independent vasodilators, ACh
and SNP, respectively, and enhanced constrictions in
response to the α1-adrenoceptor agonist PE [3,4,19]. Our
in vivo study also demonstrated the changes in vascular
activities of diabetic rats in the same direction (Fig. 1). In
normal endothelial cells, NO is synthesized and released to
maintain vascular homeostasis, especially the response to
ACh. Vascular endothelial cell dysfunction in diabetes has
been proposed to cause by oxidative stress. Hyperglycemia,
AGEs, free fatty acid, and oxidized low-density lipoprotein
have been shown to increase endothelial NADPH oxidase
activity resulting in free radical production [20]. The
decrease in vascular response to SNP, an endotheliumindependent vasodilator, indicated the change in vascular
smooth muscle function in diabetic rats as well. For the
increase in vascular smooth muscle response to the α1
-adrenoceptor agonist PE in diabetic rats, the actual
mechanism is unclear but may partly be due to the
deficiency of endothelial function in producing NO, a
vasodilator