Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes

Prostaglandins (PGs) generated by the enzyme cyclooxygenase (COX) have been implicated in the pathological renal hemodynamics and structural alteratio ns in diabetes mellitus, but the role of individual COX isoenzymes in diabe tic nephropathy remains unknown. We explored COX-I and COX-2 expression and hemodynamic responses to the COX-1 inhibitor valeryl salicylate (VS) or th e COX-2 inhibitor NS338 in moderately hyperglycemic, streptozotocin-diabeti c (D) and control (C) rats. Immunoreactive COX-2 was increased in D rats co mpared with C rats and normalized by improved glycemic control. Acute syste mic administration of NS398 induced no significant changes in mean arterial pressure and renal plasma flow in either C or D rats but reduced glomerula r filtration rate in D rats, resulting in a decrease in filtration fraction . VS had no effect on renal hemodynamics in D rats. Both inhibitors decreas ed urinary excretion of PGE(2). However, only NS398 reduced excretion of th romboxane AL. In conclusion, we documented an increase in renal cortical CO X-2 protein expression associated with a different renal hemodynamic respon se to selective systemic COX-2 inhibition in D as compared with C animals, indicating a role of COX-2-derived PG in pathological renal hemodynamic cha nges in diabetes.