(Hypertension. 1996;27:382-391.)
© 1996 American Heart Association, Inc.
Articles |
Preglomerular Sudanophilia in L-NAME Hypertensive Rats
Involvement of Endothelin
Presented in part at the 27th and 28th Annual Meetings of the American Society of Nephrology, held in Orlando, Fla, October 26-29, 1994, and in San Diego, Calif, November 5-8, 1995, respectively, and published in abstract form (J Am Soc Nephrol. 1994;5:535; J Am Soc Nephrol. 1995;6:619).
From the Groupe Rein et Hypertension, Hôpital Saint-Charles, Montpellier, France.
Correspondence to Daniel Casellas, PhD, Groupe Rein et Hypertension, Hôpital Saint-Charles, 34295 Montpellier, Cédex 5, France.
Abstract To characterize alterations of renal vessels
occurring during systemic hypertension elicited in rats by 5, 10, and
25 days of treatment by the nitric oxide synthase inhibitor
NG-nitro-L-arginine methyl
ester (L-NAME) (20 mg/kg daily), preglomerular
vasculatures, consisting of arcuate arteries and their
branches, interlobular arteries, and afferent arterioles, were isolated
by HCl maceration. Blockade of nitric oxide synthase significantly
increased tail-cuff systolic blood pressure by 21±2% and
42±3% after 5 and 25 days, respectively. Medias of hypertensive
arcuate arterial branches and interlobular arteries
but not of afferent arterioles had focal deposits of Sudan
black–positive lipid droplets. At 25 days, vessel wall thickness
increased by 72±6% along the sudanophilic areas.
Immunostaining of sudanophilic lesions with a panel of
antibodies unveiled medial cell proliferation, macrophage
invasion, immunoreactive vascular cell adhesion molecule-1, and
low-density lipoprotein. The frequency of sudanophilic
lesions increased with time to affect 26±2% and 36±3% of
arcuate arterial branches and interlobular
arteries, respectively, at 25 days. Hypertensive L-NAME–treated
rats developed glomerular injury probed by
albuminuria and glomerular
immunostaining for 
-smooth muscle actin.
Administration of the nonselective endothelin antagonist
bosentan (30 mg/kg daily) blunted the development of sudanophilic
lesions during L-NAME treatment without affecting arterial
hypertension or degree of glomerular injury. Therefore,
L-NAME hypertension leads to rapid development of focal, inflammatory,
proliferative, and sudanophilic lesions along
preglomerular vessels, suggesting
atherosclerosis-like processes. Furthermore,
endothelin is a likely mediator in the development of these lesions.
Key Words: nitric oxide • bosentan • losartan • renal arteries • atherosclerosis • glomerulopathy • L-NAME
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