Ameliorated glomerular injury in mice overexpressing brain natriuretic peptide with renal ablation.
Brain natriuretic peptide (BNP) is a cardiac hormone produced by the ventricle, and its secretion is markedly increased in heart failure, hypertension, and renal failure. Transgenic mice that overexpress BNP in the liver (BNP-Tg) were recently generated, resulting in low BP. To elucidate the role of BNP in renal pathophysiology, the effect of chronic excess of BNP in transgenic mice on glomerular injury after subtotal nephrectomy induced by resection of the renal poles was examined. After nephrectomy, glomerular cross-sectional areas in control nontransgenic mice markedly increased as compared with those in sham-operated mice (+81 +/- 7%), whereas there was only a modest increase in BNP-Tg (+10 +/- 6%). Expansion of the mesangial area and increase in the intraglomerular cell number were also inhibited in BNP-Tg. Glomerular expressions of transforming growth factor-beta and fibronectin were increased with hypertrophy and were significantly suppressed in BNP-Tg. Furthermore, increases in the urinary albumin excretion and BP were significantly ameliorated in BNP-Tg. Chronic hydralazine treatment in nephrectomized nontransgenic mice failed to inhibit glomerular hypertrophy. These findings indicate that the chronic excess of BNP in mice ameliorates glomerular hypertrophy and mesangial expansion after renal ablation. The results also suggest that the observed effects of natriuretic peptides under reduced renal mass are not due merely to systemic BP reduction and may be therapeutically applicable in various renal diseases.
Kasahara
Masato
M
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Mukoyama
Masashi
M
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Sugawara
Akira
A
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Makino
Hisashi
H
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Suganami
Takayoshi
T
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Ogawa
Yoshihiro
Y
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Nakagawa
Masayo
M
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Yahata
Kensei
K
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Goto
Masahisa
M
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Ishibashi
Rieko
R
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Tamura
Naohisa
N
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Tanaka
Issei
I
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Nakao
Kazuwa
K
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001769:Blood / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D006830:Hydralazine / Q000494:pharmacology; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic / Q000235:genetics; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism*; D009392:Nephrectomy; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014556:Urine / Q000737:chemistry
D000959:Antihypertensive Agents; D005353:Fibronectins; D016212:Transforming Growth Factor beta; D020097:Natriuretic Peptide, Brain; D006830:Hydralazine