Dietary salt loading decreases the expressions of neuronal-type nitric oxide synthase and renin in the juxtaglomerular apparatus of angiotensinogen gene-knockout mice.
The present study investigates whether neuronal type nitric oxide synthase (N-NOS) in the macula densa participates in the regulation of renal renin expression during altered dietary salt intake in angiotensinogen gene-knockout (Atg-/-) mice. Wild-type (Atg+/+) and Atg+/+ mice were fed a low-salt (0.04% NaCl), normal-salt (0.3% NaCl), or high-salt (4% NaCl) diet for 2 wk. Histochemical staining for NADPH diaphorase (NADPHd) and renin were analyzed morphometrically. Levels of N-NOS and renin mRNA in renal cortical tissues were determined by reverse transcription-PCR and Northern blot analysis, respectively. In animals fed a normal-salt diet, the renal expressions of N-NOS and renin were markedly increased in Atg-/- mice compared with Atg+/+ mice. When mutant 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. These changes were paralleled by decreases in renal renin-immunoreactive areas and the levels of renin mRNA. On the other hand, salt restriction did not produce further significant increases in the renal N-NOS and renin expressions in mutant mice, whereas a parallel inverse relationship was observed between these enzyme expressions and the levels of salt intake in wild-type mice. These results suggest that the N-NOS expression in the macula densa is inversely regulated by salt intake and that the enzyme activity is functionally linked to renal renin production. Salt-modulated renal N-NOS and renin expressions are independent on angiotensin formation in Atg-/- mice.
Kihara
M
M
Department of Internal Medicine II, Yokohama City University, Japan.
Umemura
S
S
Yabana
M
M
Sumida
Y
Y
Nyui
N
N
Tamura
K
K
Kadota
T
T
Kishida
R
R
Murakami
K
K
Fukamizu
A
A
Ishii
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D007150:Immunohistochemistry; D007606:Juxtaglomerular Apparatus / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D007686:Kidney Tubules, Distal / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009474:Neurons / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012083:Renin / Q000187:drug effects* / Q000235:genetics; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D013599:Systole
D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D019001:Nitric Oxide Synthase; D012083:Renin