title: High-protein-induced glomerular hyperfiltration is independent of the tubuloglomerular feedback mechanism and nitric oxide synthases.
abstract: A high protein intake is associated with increased glomerular filtration rate (GFR), which has been suggested to be mediated by reduced signaling of the tubuloglomerular feedback (TGF) mechanism. Nitric oxide (NO) has been shown to contribute to high protein-induced glomerular hyperfiltration, but the specific NO synthase (NOS) isoform responsible is not clear. In this study, a model for high-protein-induced hyperfiltration in conscious mice was developed. Using this model, we investigated the role of TGF using adenosine A(1)-receptor knockout mice lacking the TGF mechanism. Furthermore, the role of the different NOS isoforms was studied using neuronal-, inducible-, and endothelial-NOS knockout mice, and furthermore, wild-type mice acutely administered with the unspecific NOS inhibitor N(ω)-nitro-l-arginine methyl ester (100 mg/kg). GFR was measured consecutively in mice given a low-protein diet (8% casein) for 10 days, followed by a high-protein diet (50% casein) for 10 days. All mice developed high protein-induced hyperfiltration to a similar degree. These results demonstrate that high protein-induced glomerular hyperfiltration is independent of the TGF mechanism and NOS isoforms.
authors.affiliation: Dept. of Medical Cell Biology, Uppsala Univ., Biomedical Center, Box 571, SE-751 23 Uppsala, Sweden. johan.sallstrom@mcb.uu.se
authors.forename: Johan
authors.initials: J
authors.lastname: Sällström
authors.forename: Mattias
authors.initials: M
authors.lastname: Carlström
authors.forename: Johan
authors.initials: J
authors.lastname: Olerud
authors.forename: Bertil B
authors.initials: BB
authors.lastname: Fredholm
authors.forename: Mattias
authors.initials: M
authors.lastname: Kouzmine
authors.forename: Stellan
authors.initials: S
authors.lastname: Sandler
authors.forename: A Erik G
authors.initials: AE
authors.lastname: Persson
mesh_terms: D000818:Animals; D004044:Dietary Proteins; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D025461:Feedback, Physiological; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D007674:Kidney Diseases / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000201:enzymology / Q000503:physiopathology; D007684:Kidney Tubules / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000172:deficiency / Q000235:genetics; D013997:Time Factors
chemical_list: D004044:Dietary Proteins; D004791:Enzyme Inhibitors; D043682:Receptor, Adenosine A1; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse; D019331:NG-Nitroarginine Methyl Ester