High
dietary protein (HP) intake is a risk factor for
chronic kidney disease (CKD). HP intake is associated with the development of
albuminuria and glomerulosclerosis in uninephrectomized rats. In such rats, we investigated whether HP intake induces endothelial dysfunction. Male Wistar rats were divided into
sham-operated rats fed a standard-
protein diet,
sham-operated rats fed a
high-protein diet, uninephrectomized rats fed a standard-
protein diet (NxSP) and uninephrectomized rats fed a
high-protein diet (NxHP) (n=8 each). One week
after treatment, endothelial function and urinary
albumin excretion (UAE) were measured.
Protein expression, phosphorylation at
serine residue 1177 and uncoupling of
endothelial nitric oxide synthase (eNOS), and
mRNA expression of
NADPH oxidase components were assessed in the aorta. NxHP rats showed
hypertriglyceridemia and modest
hyperhomocysteinemia. Endothelial function was significantly lower, and UAE was significantly higher in NxHP rats compared with the other groups (P<0.01 each), although there was no difference in
creatinine clearance between NxSP and NxHP rats. Expression levels, phosphorylation and the dimer/monomer ratio of eNOS did not differ among the four groups. HP intake did not modify p22phox and p47phox expression levels in uninephrectomized rats. In conclusion, HP intake induced endothelial dysfunction and enhanced
albuminuria in uninephrectomized rats, inde-pendent of renal function, suggesting that HP intake may cause the development of
cardiovascular disease associated with CKD.