Diabetes-induced microvascular dysfunction in the hydronephrotic kidney: Role of nitric oxide

Background. Renal hemodynamics in early diabetes are characterized by pregl omerular and postglomerular vasodilation and increased glomerular capillary pressure, leading to hyperfiltration. Despite intensive research, the etio logy of the renal vasodilation in diabetes remains a matter of debate. The present study investigated the controversial role of nitric oxide (NO) in t he renal vasodilation in streptozotocin-induced diabetic rats. Methods. In the renal microcirculation, basal tone and response to NO synth ase blockade were studied using the in vivo hydronephrotic kidney technique . L-arginine analog N-nitro-L-arginine methyl ester (L-NAME) was administer ed locally to avoid confounding by systemic blood pressure effects. The exp ression of endothelial NO synthase (eNOS) was investigated in total kidney by immunocytochemistry and in isolated renal vascular trees by Western blot ting. Urinary excretion of nitrites/nitrates was measured. Results. Diabetic rats demonstrated a significant basal vasodilation of all preglomerular and postglomerular vessels versus control rats. Vasoconstric tion to L-NAME was significantly increased in diabetic vessels. After high- dose L-NAME, there was no difference in diameter between diabetic and contr ol vessels, suggesting that the basal vasodilation is mediated by NO. Immun ocytochemically, the expression of eNOS was mainly localized in the endothe lium of preglomerular and postglomerular vessels and glomerular capillaries , and was increased in the diabetic kidneys. Immunoblots on isolated renal vascular trees revealed an up-regulation of eNOS protein expression in diab etic animals. The urinary excretion of nitrites/nitrates was elevated in di abetic rats. Conclusion. The present study suggests that an up-regulation of eNOS in the renal microvasculature. resulting in an increased basal generation of NO, is responsible for the intra renal vasodilation characteristic of early dia betes.