Hyperglycemia induced by chronic i.p. and oral glucose loading leads to hypertension through increased Na+-retention in proximal tubule

Abstract

Feeding animals glucose, fructose, sucrose, and fat-enriched diets can lead to diet-induced hyperglycemia, severity of which largely depends on type and concentration of nutrients used and length of dietary intervention. As a strategy of dietary intervention, we adopted glucose-enriched diet, drinking water, and intraperitoneal (i.p.) glucose injection at the dose previously determined to be effective to establish a sustained hyperglycemia over a period of 2 weeks. In our current study, we used 4 groups of Sprague Dawley rats: control, glucose-treated, glucose+tempol, and glucose+captopril-treated groups. Our study demonstrated that glucose levels gradually started to increase from day 3, and reached to the highest levels (321 mg dl⁻¹) at day 12 and maintained similar levels until the end of the study on day 14 in glucose treated-group compared to control. However, tempol- and captopril-treated groups showed significantly high glucose levels in only second week. Plasma insulin level has been significantly increased in glucose-treated animals but not in tempol- and captopril-treated groups when compared to control. We also observed elevated blood pressure (BP) in glucose-treated group compared to control, which can be attributed to increased Ang II production from 46.67 pg.ml⁻¹ to 99 pg.ml⁻¹ (control vs. glucose), increased oxidative stress in cortical proximal tubule (PT), decreased urine flow, and increased expression and activity of PT-specific α₁-subunit of Na⁺-K⁺-ATPase in renal cortex, the latter is responsible for increased sodium reabsorption from epithelial cells of PT into peritubular capillaries, leading to increased blood volume and eventual blood pressure. All these events are reversed in captopril- and tempol-treated animals.

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