The development and progression of renal damage in Streptozotocin-Type1 Diabetes Mellitus under Goldblatt renovascular hypertension and high-salt condition




Sima, Carmen Aurelia

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Under normotensive conditions, the progressive loss of renal function in diabetes mellitus is very slow. Since hypertension accelerates many forms of renal disease, we assessed the progression of nephropathy in Streptozotocin-induced type 1 diabetes mellitus under renin-mediated hypertension condition. We investigated the diabetic “salt paradox” as a modifiable susceptibility factor for renal damage. Since hyperfiltration occurs in early diabetes, the reduction of glomerular filtration rate due to an increased salt intake could be mediated by increased tubuloglomerular feedback sensitivity. We compared intact-hypertensive versus diabetic-hypertensive Long-Evans rats under normal and increased salt intake, 1 and 2.5% by weight of food eaten, respectively. Weekly 24-h blood pressure records were acquired by telemetry during the six months of the experiment. Target mean blood glucose of ~ 25 mmol/L was maintained by suboptimal insulin implants. Systolic blood pressure increased after induction of hypertension but was not affected by diabetes or increased salt intake, either alone or together. Autoregulation was highly efficient in both intact and diabetic rats. Nephropathy was scored by histology in the clipped and non-clipped kidneys at the end of the protocol. The non-clipped kidney, which was exposed to hypertension, showed a linear pressure-dependent glomerular injury in both intact and diabetic rats. The best fit line describing the linear relationship between pressure load and injury was shifted toward lower blood pressure in diabetic rats. Over the time course of our experiments, injury was entirely pressure dependent in intact and diabetic rats. Diabetes mellitus increased the susceptibility of the kidney to injury, but independent of blood pressure. Increased salt intake affected neither blood pressure nor renal susceptibility to hypertensive injury.



Diabetes mellitus, salt sensitivity, salt paradox, Goldblatt hypertension, renal autoregulation