Role of angiotensin II in the tubulointerstitial fibrosis of obstructive nephropathy.
Chronic unilateral ureteral obstruction results in interstitial fibrosis of the affected kidney. Both an angiotensin-converting enzyme inhibitor, enalapril, and an angiotensin II receptor antagonist, SC-51316, ameliorate the increased production of extracellular matrix protein in the tubulointerstitium of the obstructed kidney. Blockade of angiotensin II synthesis or inability of angiotensin II to bind to its receptor lessened the increased levels of mRNA for transforming growth factor-beta and collagen IV found in the obstructed kidney of untreated rats. A monocyte/macrophage infiltration was present in the obstructed kidney of untreated rats or rats treated with the angiotensin II receptor antagonists. In contrast, this infiltrate was almost completely absent in the obstructed kidney of rats treated with enalapril. The reason for this different effect of enalapril compared with the angiotensin II receptor antagonist on the macrophage infiltrate seen in obstructive nephropathy has not been elucidated. We conclude that both an angiotensin-converting enzyme inhibitor (enalapril) and a receptor antagonist of angiotensin II ameliorate the tubulointerstitial fibrosis that follows complete unilateral ureteral obstruction in the rat. We suggest that an increased level of angiotensin II has a major role in the development of tubulointerstitial fibrosis following ureteral obstruction.
Klahr
S
S
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Ishidoya
S
S
Morrissey
J
J
D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D003094:Collagen / Q000378:metabolism; D004656:Enalapril / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013777:Tetrazoles / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000235:genetics; D014230:Triazoles / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000150:complications*
D057911:Angiotensin Receptor Antagonists; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D014230:Triazoles; D000804:Angiotensin II; C075064:SC 51316; D004656:Enalapril; D003094:Collagen