タナカ　リョウジロウ   Ryojiro Tanaka   田中　亮二郎    所属   川崎医科大学  医学部 臨床医学　小児科学    職種   特任教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Angiotensin converting enzyme inhibitor modulates glomerular function and structure by distinct mechanisms.
掲載誌名	正式名：Kidney international 略　 称：Kidney Int ISSNコード：00852538/00852538
掲載区分	国外
巻・号・頁	45(2),pp.537-43
著者・共著者	R Tanaka, V Kon, T Yoshioka, I Ichikawa, A Fogo
発行年月	1994/02
概要	Rats with puromycin aminonucleoside (PAN) nephrosis were given either angiotensin I converting enzyme inhibitor (ACEI), angiotensin II type 1 receptor antagonist (Ang IIRA), or no treatment for four weeks and were then monitored for an additional 12 weeks. In untreated PAN rats, proteinuria reached a maximum at two weeks (271 +/- 38 mg/day). Proteinuria in this early phase was markedly attenuated by ACEI (96 +/- 35 mg/day, P < 0.01), but unaffected by Ang IIRA (306 +/- 34 mg/day). Acute administration of a bradykinin antagonist substantially dampened the antiproteinuric effect of ACEI in PAN rats, resulting in an average increase in proteinuria of 41 +/- 14% in ACEI-treated rats (P < 0.05, ACEI vs. ACEI+bradykinin antagonist). Acute phase therapy for four weeks with ACEI or Ang IIRA did not attenuate subsequent glomerulosclerosis. Separate groups of PAN rats with similar degree of glomerulosclerosis, assessed at 16 weeks after PAN by renal biopsy, were then treated as follows: ACEI [50 mg/liter drinking water (DW), or 200 mg/liter DW], Ang IIRA (20 mg/liter DW, or 80 mg/liter DW) or no treatment, starting after renal biopsy. Whereas glomerulosclerosis increased from biopsy to autopsy at 28 weeks with emergence of low grade proteinuria in untreated PAN rats, proteinuria was absent and glomerulosclerosis was ameliorated or reversed in ACEI and Ang IIRA groups. The results indicate that the early phase proteinuria of PAN nephropathy is independent of Ang II, and that the antiproteinuric effect of ACEI is, at least in part, channeled through activation of bradykinin, whereas the subsequent progression of glomerulosclerosis is caused by a mechanism involving endogenous Ang II actions.(ABSTRACT TRUNCATED AT 250 WORDS)
DOI	10.1038/ki.1994.69
PMID	8164442