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(Hypertension. 1996;27:382-391.)
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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).

Nathalie Bouriquet; Madeleine Dupont; Abderraouf Herizi; Albert Mimran; Daniel Casellas

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 N^G-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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