ABERRANT RENAL VASCULAR MORPHOLOGY AND RENIN EXPRESSION IN MUTANT MICE LACKING ANGIOTENSIN-CONVERTING ENZYME

To determine whether angiotensin-converting enzyme plays a role in the development and maintenance of normal renal architecture, the renal m orphology of 10- to 12-month-old female mice homozygous for a disrupti on of the converting enzyme gene was compared with that of age-matched wild-type mice. Tubular obstruction, dilatation, and atrophy were pre sent in all kidneys from the homozygous mutant mice but absent in wild types; two kidneys from 4 mutant mice but none from the wild types we re hydronephrotic. The entire arterial vascular tree, microdissected f rom mice with no converting enzyme, was grossly distorted in compariso n to the vasculature of wild-type mice; all intrarenal arterial vessel s were widened and thickened, including the terminal (afferent) arteri oles. In wild-type mice kidneys, renin-positive cells were detected ex clusively in a juxtaglomerular localization. In contrast, abnormal dis tribution of renin immunostaining was observed in mice without convert ing enzyme; scattered renin-positive cells were seen along the arteria l vessels, often in a perivascular localization, and interstitial reni n-positive cells surrounded glomeruli. Kidney renin mRNA was increased more than 32-fold in the mutant mice compared with wild types. Northe rn blot analysis revealed that this increase included the accumulation of large amounts of smaller renin RNA transcripts. In summary, mice l acking the converting enzyme exhibit abnormal renal vessels and tubule s. Renin synthesis is increased, accompanied by the presence of small renin mRNA species, and renin is present mainly in interstitial and pe rivascular cells. We conclude that angiotensin-converting enzyme is ne cessary to preserve normal kidney architecture and the normal pattern of renin expression.