(Hypertension. 1997;29:216.)
© 1997 American Heart Association, Inc.
Arthur C. Corcoran Memorial Lecture |
Aberrant Renal Vascular Morphology and Renin Expression in Mutant Mice Lacking Angiotensin-Converting Enzyme
From the Division of Pediatric Nephrology, Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville, and Departments of Pathology (J.H.K., O.S.) and Medicine (J.H.K.), University of North Carolina, Chapel Hill.
Correspondence to R. Ariel Gomez, MD, Chief, Pediatric Nephrology Division, Department of Pediatrics, University of Virginia Health Sciences Center, 300 Lane Rd, MR4 Bldg, Room 2001, Charlottesville, VA 22908
To determine whether angiotensin-converting enzyme plays a role in the development and maintenance of normal renal architecture, the renal morphology of 10- to 12-month-old female mice homozygous for a disruption of the converting enzyme gene was compared with that of age-matched wild-type mice. Tubular obstruction, dilatation, and atrophy were present 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 were hydronephrotic. The entire arterial vascular tree, microdissected from mice with no converting enzyme, was grossly distorted in comparison to the vasculature of wild-type mice; all intrarenal arterial vessels were widened and thickened, including the terminal (afferent) arterioles. In wild-type mice kidneys, renin-positive cells were detected exclusively in a juxtaglomerular localization. In contrast, abnormal distribution of renin immunostaining was observed in mice without converting enzyme; scattered renin-positive cells were seen along the arterial vessels, often in a perivascular localization, and interstitial reninpositive cells surrounded glomeruli. Kidney renin mRNA was increased more than 32-fold in the mutant mice compared with wild types. Northern blot analysis revealed that this increase included the accumulation of large amounts of smaller renin RNA transcripts. In summary, mice lacking the converting enzyme exhibit abnormal renal vessels and tubules. Renin synthesis is increased, accompanied by the presence of small renin mRNA species, and renin is present mainly in interstitial and perivascular cells. We conclude that angiotensin-converting enzyme is necessary to preserve normal kidney architecture and the normal pattern of renin expression.
Key Words: vessels • arterioles • kidney • knockout mice • renovascular
Abbreviations: Ang = angiotensin • AT1 = angiotensin II type 1 receptor • PCR = polymerase chain reaction • RAS = renin-angiotensin system
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