Published online before print August 5, 2002, doi: 10.1161/01.CIR.0000027105.02327.48
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(Circulation. 2002;106:1165.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Distinct Renal Injury in Early Atherosclerosis and Renovascular Disease
From the Departments of Internal Medicine, Divisions of Hypertension (A.R.C., J.D.K., L.O.L.) and Cardiovascular Diseases (M.R.-P., A.L.), Physiology and Biophysics (J.C.R.), and Laboratory Medicine and Pathology (J.P.G.), Mayo Clinic, Rochester, Minn; the Department of Medicine, University of Naples, Italy (C.N.); and the Department of Medicine, University of California, San Diego, Calif (C.N.).
Correspondence to Lilach O. Lerman, MD, PhD, Division of Hypertension, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail lerman.lilach{at}mayo.edu
Background— Atherosclerotic renovascular disease may augment deterioration of renal function and ischemic nephropathy compared with other causes of renal artery stenosis (RAS), but the underlying mechanisms remain unclear. This study was designed to test the hypothesis that concurrent early atherosclerosis and hypoperfusion might have greater early deleterious effects on the function and structure of the stenotic kidney.
Methods and Results— Regional renal hemodynamics and function at baseline and during vasoactive challenge (acetylcholine or sodium nitroprusside) were quantified in vivo in pigs by electron-beam computed tomography after a 12-week normal (n=7) or hypercholesterolemic (HC, n=7) diet, RAS (n=6), or concurrent HC and a similar degree of RAS (HC+RAS, n=7). Flash-frozen renal tissue was studied ex vivo. Basal cortical perfusion and single-kidney glomerular filtration rate (GFR) were decreased similarly in the stenotic RAS and HC+RAS kidneys, but tubular fluid reabsorption was markedly impaired only in HC+RAS. Perfusion responses to challenge were similarly blunted in the experimental groups. Stimulated GFR increased in normal, HC, and RAS (38.3±3.6%, 36.4±7.6%, and 60.4±9.3%, respectively, P<0.05), but not in HC+RAS (6.5±15.1%). These functional abnormalities in HC+RAS were accompanied by augmented perivascular, tubulointerstitial, and glomerular fibrosclerosis, inflammation, systemic and tissue oxidative stress, and tubular expression of nuclear factor-
B and inducible nitric oxide synthase.
Conclusions— Early chronic HC+RAS imposes distinct detrimental effects on renal function and structure in vivo and in vitro, evident primarily in the tubular and glomerular compartments. Increased oxidative stress may be involved in the proinflammatory and progrowth changes observed in the stenotic HC+RAS kidney, which might potentially facilitate the clinically observed progression to end-stage renal disease.
Key Words: atherosclerosis • kidney • regional blood flow
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