Ameliorated glomerular injury in mice overexpressing brain natriuretic peptide with renal ablation.

Abstract

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.

• Authors: Masato Kasahara, Masashi Mukoyama, Akira Sugawara, Hisashi Makino, Takayoshi Suganami, Yoshihiro Ogawa, Masayo Nakagawa, Kensei Yahata, Masahisa Goto, Rieko Ishibashi, Naohisa Tamura, Issei Tanaka, Kazuwa Nakao
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 11 Issue 9 Pg. 1691-1701 (Sep 2000) ISSN: 1046-6673 [Print] United States
• PMID: 10966494 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Fibronectins
• Transforming Growth Factor beta
• Natriuretic Peptide, Brain
• Hydralazine

Topics

• Animals
• Antihypertensive Agents (pharmacology)
• Blood (metabolism)
• Blood Pressure (drug effects, physiology)
• Fibronectins (metabolism)
• Hydralazine (pharmacology)
• Immunohistochemistry
• Kidney (pathology)
• Kidney Glomerulus (metabolism, pathology)
• Mice
• Mice, Inbred Strains
• Mice, Transgenic (genetics)
• Natriuretic Peptide, Brain (genetics, metabolism)
• Nephrectomy
• Reference Values
• Transforming Growth Factor beta (metabolism)
• Urine (chemistry)