Free radical scavenging decreases endothelin-1 excretion and glomerular albumin permeability during type 1 diabetes

Increased renal endothelin-1 (ET-1) production and an ET_A receptor-dependent increase in glomerular albumin permeability (P_alb) accompany type 1 diabetes mellitus (T1D). We hypothesized that T1D-induced oxidative stress contributes to renal ET-1 production and glomerular P_alb Male rats with streptozotocin-induced T1D were provided free access to drinking water without additives (T1D rats) or containing the free radical scavenger tempol (1 mmol/L; T1D+Tempol). After 3 weeks, T1D+Tempol rats displayed lower urinary excretion of thiobarbituric acid reactive substances and glomerular superoxide production (dihydroethidium staining) compared to T1D rats. Urinary ET-1 excretion and inner medullary (but not cortical or outer medullary) prepro-ET-1 mRNA expression were lower in the T1D+Tempol group than in the T1D group. P_alb, measured as the change in volume of isolated glomeruli upon exposure to oncotic gradients of albumin, was significantly lower in the T1D+Tempol group than in the T1D group. Tempol treatment did not alter protein excretion or creatinine clearance. These data support the postulate that oxidative stress contributes to glomerular P_alb and renal ET-1 production during the early phase of type 1 diabetes.