Acute IP Furosemide Increases Medullary PO2 in The Diabetic Rat Kidney

Abstract

We recently observed medullary hypoxia during SGLT (sodium glucose linked transport) inhibition in the diabetic rat kidney. Underlying mechanisms are unclear but may reflect compensatory increases in sodium reabsorption in distal nephron segments, such as the medullary thick ascending limb (mTAL), where sodium transport is less efficient. To test this hypothesis, we investigated the impact of NKCC (sodium/potassium/chloride) co‐transporter inhibition on renal oxygen metabolism in the diabetic rat kidney.Diabetes was induced by intraperitoneal (IP) STZ (50mg/kg) injection in Sprague Dawley rats (n=11), 2 weeks prior to experimentation. Animals were surgically prepared for intravenous infusion of [3H]Inulin and [14C]PAH, the IP delivery of furosemide (NKCC inhibitor; 3mg/Kg) and the measurement of mean arterial pressure (MAP), left kidney function and medullary (M) PO2 (Clark electrode). Data± SEM was analyzed using a two‐way RM ANOVA. Baseline MAP, transported sodium (TNa), total kidney oxygen consumption (QO2), and MPO2 was 107±4 mmHg, 189±23 µmol/min, 23±3 µmol/min and 26±2 mmHg, respectively. IP furosemide, had no effect on MAP, reduced TNa and QO2 to 58±7 µmol/min and 8±2 µmol/min respectively and increased MPO2 to 36±2 mmHg (all P<0.05).Sodium transport via NKCC is clearly a major consumer of oxygen in the diabetic rat kidney. Moreover, the furosemide‐induced increase in MPO2 is in vast contrast to the reduction in medullary PO2, previously observed during SGLT inhibition. These data provide evidence that medullary hypoxia during SGLT inhibition in the diabetic rat kidney results from the diversion of TNa to the mTAL where sodium transport is less efficient.