Free radical scavenging decreases endothelin‐1 excretion and glomerular albumin permeability during type 1 diabetes. Issue 24 (30th December 2016)

• Record Type: Journal Article
• Authors: Saleh, Mohamed A.; De Miguel, Carmen; Stevens, David I.; Carmines, Pamela K.; Pollock, David M.; Pollock, Jennifer S.
• Is Part Of: Physiological reports. Volume 4:Issue 24(2016)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2016-12-30
• Subjects: Diabetes -- ET‐1 -- glomerular permeability -- tempol; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.13055
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: 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. Abstract : This study provides evidence that in vivo scavenging of free radicals decreases glomerular Palb in early diabetes and ameliorates the renal inner medullary synthesis and urinary excretion of endothelin‐1 ( ET‐1). Therefore, antioxidant treatment attenuates early changes in renal function during diabetes, at least in part, via the ET‐1 pathway.