Pinitol ameliorates impaired pressure‐natriuresis in experimental diabetes (1063.5)

Abstract

Pressure‐induced natriuresis is a physiological protective mechanism that counteracts increased blood pressure with increased diuresis and natriuresis. We evaluated whether diabetes would affect this mechanism and if pinitol, an antidiabetic compound , could prevent and/or reverse any alterations. We induced diabetes by a single injection of 70 mg/kg streptozotocin (i.p) and 2‐month and 4‐months diabetic rats (Diab) compared to time‐matched euglycemic rats (eugly). We employed the Roman‐Cowley model of pressure‐natriuresis (P‐N) in male Wistar rats. We measured fractional excretion of sodium (FENa) and glomerular filtration rate (GFR), filtration fraction (FF), renal blood flow (RBF) and renal vascular resistance (RVR). We have shown that STZ‐diabetes blunts pressure‐natriuresis, in animals submitted to similar increases in renal perfusion pressure, after 2‐months (eugly‐ FENa from 0.5± 0.4 to 3.8±1.5% during P‐N vs diab‐ 0.4 ±0.2% to 0.8±0.2%) and after 4 months pressure‐natriuresis is completely absent (FENa from 0.16±0.04% to 0.23±0.08%). In another set of experiments, two regimens of pinitol treatments were administered to different diabetic groups. One received 20 mg/kg/12h (p.o) during 2‐months beginning 2‐months after the initial diagnosis of diabetes. The other group received the same dosage after the first day of diagnosis and was kept on this regimen during two months. The firs regimen was able to ameliorate kidney function during the P‐N period (FENa from 0.2±0.08% to 0.48±0.2%). Remarkably, the second treatment regimen further improved renal function during the pressure‐natriuresis period (FENa from 0.8±0.03% to 2.34±0.9%). Diabetes profoundly decreases kidney ability to respond to increased perfusion pressure with increased sodium excretion and 2‐month pinitol treatment is able to both reverse and especially prevent this diabetic complication.Grant Funding Source: CNPq/Brazil; FUNCAP‐CE/Brazil