These results suggest that diabetes induces hypereactivity of the rabbit renal artery to BNP by mechanisms that at least include (1) a reduced vasoconstrictor influence of arachidonic acid metabolites via cyclooxygenase 2, which is not related with changes in thromboxane A<sub>2</sub> and prostacyclin release from the arterial wall and (2) a selectively increased modulatory activity of K<sub>ATP</sub> and endothelial IK<sub>Ca</sub> channels.
After CPB, bradykinin-induced relaxation response of the ND and DM arterioles was inhibited in the presence of the specific COX-2 inhibitor NS398, but this effect was more pronounced in the diabetic patients (P < 0.05).
These data suggest that <i>1</i>) KO of COX2 in podocytes does not ameliorate diabetic kidney disease in Akita mice, and <i>2</i>) some basal level of podocyte COX2 expression in podocytes is necessary to attenuate the adverse effects of diabetes on glomerular filtration barrier function.
The products of COX-2 and LOX activities have been implicated in cytokine-mediated damage of beta-cells, so selective inhibitors of these enzymes would be expected to have a dual protective role in diabetes: they would minimize beta-cell dysfunction while maintaining insulin secretion through enhancing endogenous arachidonic acid levels.
In this study we evaluated whether diabetic conditions in vitro, such as high-glucose (HG) culture or AGE, or in vivo in animal models of diabetes can induce PTGS2 expression and activity in pancreatic islets.