title: Alterations in renal endothelial nitric oxide synthase expression by salt diet in angiotensin type-1a receptor gene knockout mice.
abstract: The effects of altered dietary salt intake and/or hydralazine-induced hypotension on renal endothelial nitric oxide synthase (eNOS) expression were determined in angiotensin type-1a receptor gene knockout (At1a-/-) and wild-type (At1a+/+) mice. In At1a-/- mice, the levels of renal cortical eNOS mRNA and protein were 5 times and 3.5 times higher, respectively, in the high-salt (4% NaCl) group than in the low-salt group (0.3% NaCl). Systemic BP of the high-salt group (105 +/- 4.4 mmHg) was significantly higher than that of the low-salt group (77.0 +/- 4.7 mmHg). When hydralazine was administered to the mutant mice fed a high-salt diet, BP was reduced to 72.5 +/- 1.3 mmHg, with decreases in the levels of renal eNOS mRNA and protein expression to about half of those found in nontreated group. Consistent with the results for eNOS mRNA and protein expression, nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity and eNOS immunoreactivity localized in the endothelium of the renal vasculature changed parallel with the amount of salt intake. In contrast to mutant mice, At1a+/+ mice did not show any changes in renal eNOS expression during the manipulation of salt intake and/or hydralazine-induced hypotension. These results suggest that At1a receptor-mediated inputs play critical roles in maintaining renal vascular eNOS expression and activity during changes in salt-water balance and systemic BP.
authors.affiliation: Department of Second Internal Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Sato
authors.forename: Minoru
authors.initials: M
authors.lastname: Kihara
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Kei
authors.initials: K
authors.lastname: Matsushita
authors.forename: Yu-Ichi
authors.initials: Y
authors.lastname: Koide
authors.forename: Koichi
authors.initials: K
authors.lastname: Tamura
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Hirawa
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Toya
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D006830:Hydralazine / Q000494:pharmacology; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012492:Salts / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D012492:Salts; D006830:Hydralazine; D012965:Sodium Chloride; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D009252:NADPH Dehydrogenase