Аннотация:At the initial stage diabetic kidney pathology appears as hyperfiltration associated with decrease in preglomerular vascular resistance. We aimed at studying endothelium-dependent relaxation in renal arteries of diabetic rats. Type 1 diabetes mellitus was induced in male Wistar rats by a single injection of streptozotocin. Six weeks later the rats demonstrated increases of relative kidney weight (2-fold), diuresis (26-fold), creatinine clearance (1.7-fold) and urine albumin/creatinine ratio (2.2-fold). Interlobar arteries were isolated and studied by wire myography technique. For comparison we studied diabetic alterations in small arteries supplying skin (saphenous), gastrocnemius muscle, diaphragm and intestine. mRNA expression levels were studied by qPCR. All arteries, except renal, showed smaller responses to acetylcholine in diabetic rats compared to controls. Contrarily, renal arteries of diabetic rats demonstrated augmented response to acetylcholine, which was not associated with higher NO production, since the augmentation persisted after NO-synthase inhibition (L-NNA) and arterial sensitivity to NO-donor (DEA-NO) was not changed in comparison to control. However, inhibition of cyclooxygenase (indomethacin) together with NO-synthase eliminated the differences; residual (EDHF-like) component did not differ between the groups. Together with smaller impact of contractile prostanoids renal arteries of diabetic rats compared to controls had higher content of COX1 mRNA, while COX2 and eNOS mRNA levels were not changed. In conclusion, in normal rat kidney contractile influence of prostanoids restricts endothelium-dependent vasorelaxation. Failure of this mechanism may be a factor in glomerular hyperfiltration and nephropathy development.