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

Increased renal endothelin-1 (ET-1) production and an ETA receptor-dependent increase in glomerular albumin permeability (Palb ) accompany type 1 diabetes mellitus (T1D). We hypothesized that T1D-induced oxidative stress contributes to renal ET-1 production and glomerular Palb 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. Palb , 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 Palb and renal ET-1 production during the early phase of type 1 diabetes.