Role of nitric oxide and angiotensin II in diabetes mellitus-induced glomerular hyperfiltration.

Abstract

The goal of this study was to determine what extent nitric oxide (NO) and/or angiotensin II (AngII) are involved in the hyperfiltration observed in rats with streptozotocin-induced diabetes mellitus. Studies were performed on anesthetized rats 7 to 10 days after the induction of diabetes. Nitro-L-arginine (LNA) was used to inhibit NO synthesis, and losartan was used to block AngII receptors. Three protocols were utilized: (i) control and diabetic rats treated with a constant infusion of LNA; (ii) control and diabetic rats treated first with a constant infusion of losartan and then LNA plus losartan; and (iii) nephrectomized control and diabetic rats treated with LNA (to evaluate the involvement of renal vasoactive factors other than AngII in the systemic response to LNA). Compared with controls, diabetics had a significantly elevated baseline GFR but the same mean arterial pressure (MAP). In Protocol i, LNA caused the same increase in MAP in both groups but only decreased the GFR in controls. In Protocol ii, losartan caused a significant increase in the GFR only in controls. The coinfusion of LNA and losartan caused no change in the GFR in controls but induced a large GFR decrease in diabetics. Losartan had no effect on MAP in either group and did not affect the LNA-induced increase in MAP in either group. The LNA-induced increase in MAP was greater in nephrectomized rats compared with that in intact rats. These data indicate that (1) neither changes in the synthesis of NO nor changes in the actions of AngII, alone, are responsible for the hyperfiltration observed in streptozotocin-induced diabetes; (2) a combined alteration in these two systems may account for diabetes-induced hyperfiltration; (3) the LNA-induced decrease in GFR in control but not in diabetic rats is an AngII-mediated event; and (4) AngII is not involved in the LNA-induced increase in MAP in either control or diabetic rats but other renal factors cannot be ruled out in this response.