title: Expression of neuronal type nitric oxide synthase and renin in the juxtaglomerular apparatus of angiotensin type-1a receptor gene-knockout mice.
abstract: Angiotensin type-1a (AT1a) receptor gene-knockout (AT1a-/-) mice exhibit chronic hypotension and renin overproduction. In the kidneys of AT1a-/- mice, the activity of neuronal type nitric oxide synthase (N-NOS) was histochemically detected by nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase (NADPHd) reaction combined with N-NOS immunohistochemistry. The localization of renin was detected by immunohistochemistry and the results were analyzed morphometrically. The levels of N-NOS and renin mRNA in the renal cortical tissue were determined by reverse transcription-PCR and Northern blot analysis, respectively. In the renal sections from wild-type mice, NADPHd activity and N-NOS immunoreactivity were localized to the discrete region of the macula densa in contact with the parent glomerulus. In contrast, N-NOS-positive macula densa cells were distributed beyond the original location of the macula densa, occasionally extending to the opposite side of the distal tubules. The mean number of N-NOS positive macula densa cells was significantly increased in AT1a-/- mice (186 per 100 glomeruli) compared with wild-type mice (65 per 100 glomeruli). AT1a-/- mice showed 1.4-times higher N-NOS mRNA levels in the renal cortical tissues than wild-type mice. The plasma renin activity was significantly higher in AT1a-/- mice (205.5 +/- 26.1 ng/ml/hr) than in wild-type mice (8.0 +/- 0.2 ng/ml/hr). The renin-positive areas per glomerulus and renal renin gene expression were 12-times and 2.6-times higher in AT1a-/- mice than in wild-type mice, respectively. These abnormalities, however, were less remarkable in AT1a-/- mice compared with angiotensinogen-knockout mice. When AT1a-/- mice were fed a high-salt diet, the signal intensity of the NADPHd reaction and the number of positively-stained macula densa cells were significantly decreased. The levels of renal cortical N-NOS mRNA were also suppressed by the treatment. Dietary salt loading produced a parallel decrease in plasma renin activity, renal renin-immunoreactive areas, and the levels of renin mRNA without affecting systemic blood pressure. These results provide evidence for the possible involvement of N-NOS at the macula densa in the increased renin production in AT1a-/- mice.
authors.affiliation: Department of Internal Medicine II, Yokohama City University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kihara
authors.forename: S
authors.initials: S
authors.lastname: Umemura
authors.forename: T
authors.initials: T
authors.lastname: Sugaya
authors.forename: Y
authors.initials: Y
authors.lastname: Toya
authors.forename: M
authors.initials: M
authors.lastname: Yabana
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: T
authors.initials: T
authors.lastname: Kadota
authors.forename: R
authors.initials: R
authors.lastname: Kishida
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.forename: A
authors.initials: A
authors.lastname: Fukamizu
authors.forename: M
authors.initials: M
authors.lastname: Ishii
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004032:Diet; D015870:Gene Expression / Q000502:physiology; D007606:Juxtaglomerular Apparatus / Q000378:metabolism* / Q000473:pathology; D007672:Kidney Cortex / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D011945:Receptors, Angiotensin / Q000172:deficiency* / Q000235:genetics; D012083:Renin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D011945:Receptors, Angiotensin; D012965:Sodium Chloride; D000803:Angiotensin I; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D012083:Renin