title: Preglomerular sudanophilia in L-NAME hypertensive rats: involvement of endothelin.
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 alpha-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.
authors.affiliation: Group Rein et Hypertension, Hopital Saint-Charles, Montpellier, France.
authors.forename: N
authors.initials: N
authors.lastname: Bouriquet
authors.forename: M
authors.initials: M
authors.lastname: Dupont
authors.forename: A
authors.initials: A
authors.lastname: Herizi
authors.forename: A
authors.initials: A
authors.lastname: Mimran
authors.forename: D
authors.initials: D
authors.lastname: Casellas
mesh_terms: D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002455:Cell Division; D016232:Endothelins / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000098:blood supply*; D050356:Lipid Metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D051381:Rats; D013194:Staining and Labeling
chemical_list: D016232:Endothelins; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester