Acute SGLT inhibition normalizes O-2 tension in the renal cortex but causes hypoxia in the renal medulla in anaesthetized control and diabetic rats

• Early stage diabetic nephropathy is characterized by glomerular hyperfiltration and reduced renal tissue PO2. Recent observations have indicated that increased tubular Na+-glucose linked transport (SGLT) plays a role in the development of diabetes-induced hyperfiltration. The aim of the present study was to determine how inhibition of SLGT impacts upon PO2 in the diabetic rat kidney. Diabetes was induced by streptozotocin in Sprague-Dawley rats 2 wk before experimentation. Renal hemodynamics, excretory function, and renal O-2 homeostasis were measured in anesthetized control and diabetic rats during baseline and after acute SGLT inhibition using phlorizin (200 mg/kg ip). Baseline arterial pressure was similar in both groups and unaffected by SGLT inhibition. Diabetic animals displayed reduced baseline PO2 in both the cortex and medulla. SGLT inhibition improved cortical PO2 in the diabetic kidney, whereas it reduced medullary PO2 in both groups. SGLT inhibition reduced Na+ transport efficiency [tubular Na+ transport (TNa)/renal O-2 consumption (QO(2))] in the control kidney, whereas the already reduced TNa/QO(2) in the diabetic kidney was unaffected by SGLT inhibition. In conclusion, these data demonstrate that when SGLT is inhibited, renal cortex PO2 in the diabetic rat kidney is normalized, which implies that increased proximal tubule transport contributes to the development of hypoxia in the diabetic kidney. The reduction in medullary PO2 in both control and diabetic kidneys during the inhibition of proximal Na+ reabsorption suggests the redistribution of active Na+ transport to less efficient nephron segments, such as the medullary thick ascending limb, which results in medullary hypoxia.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Urology and Nephrology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

diabetes

oxgen consumption

renal hypoxia

sodium-glucose linked transport

sodium transport

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