Contribution of endothelial nitric oxide synthase in the blunted renal responses to volume expansion in diabetic rats

The renal excretory responses to volume expansion (VE), by 10 % body wt, we re determined in groups of anaesthetised streptozotocin-induced diabetic ra ts with one denervated and one innervated kidney in the presence and absenc e of nitric oxide synthase (NOS) inhibitors. VE in diabetic rats increased (P < 0.001) cumulative urine sodium excretion (CuUNaV) to 104 +/- 9 and 69 +/- 6 mu mol min(-1) (g kidney wt)(-1) in the denervated and in the innerva ted kidneys, respectively, which were both less (P < 0.001) than in the non -diabetic rats, at 225 +/- 14 and 148 +/- 14 mu mol min(-1) (g kidney wt)(- 1), respectively, in the denervated and the innervated kidney. The non-sele ctive NOS inhibitor, N-G-nitrO-L-arginine-methylester (L-NAME) given to the diabetic rats with intact renal innervation enhanced CuUNaV after VE by 43 % (P < 0.001), while the combination of L-NAME and renal denervation restor ed CuUNaV to a value comparable to that of non-diabetic rats. In diabetic r ats treated with either a relatively selective inhibitor for the neuronal i soform of NOS, 7-nitroindazole, or a relatively selective inhibitor for the inducible isoform of NOS, aminoguanidine, CuUNaV after VE was similar to t he untreated diabetic rats irrespective of whether or not the renal nerves were present. This investigation demonstrated that NO production contribute d, at least partly, to the depressed ability to excrete a saline load in di abetes mellitus. The endothelial isoform of NOS was most probably responsib le for generating NO which caused the blunted excretory responses. The abil ity of NO to attenuate the excretory responses to volume expansion was an a ction independent of the renal innervation status.