title: High dietary protein intake induces endothelial dysfunction in uninephrectomized rats.
abstract: 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.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki 701-0192, Japan.
authors.forename: Tamehachi
authors.initials: T
authors.lastname: Namikoshi
authors.forename: Naruya
authors.initials: N
authors.lastname: Tomita
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Takeo
authors.initials: T
authors.lastname: Sakuta
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kuwabara
authors.forename: Hajime
authors.initials: H
authors.lastname: Nagasu
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yorimitsu
authors.forename: Tamaki
authors.initials: T
authors.lastname: Sasaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Kashihara