Preglomerular Sudanophilia in L-NAME Hypertensive Rats: Involvement of Endothelin

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1996-03, Vol.27 (3), p.382-391
• Main Authors: Bouriquet, Nathalie, Dupont, Madeleine, Herizi, Abderraouf, Mimran, Albert, Casellas, Daniel
• Format: Article
• Language: English
• Subjects: Animals; Arginine - administration & dosage; Arginine - analogs & derivatives; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Division; Endothelins - metabolism; Experimental diseases; Hypertension - chemically induced; Hypertension - metabolism; Hypertension - physiopathology; Kidney Glomerulus - blood supply; Lipid Metabolism; Male; Medical sciences; NG-Nitroarginine Methyl Ester; Rats; Staining and Labeling
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.27.3.382

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 -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 plus/minus 2% and 42 plus/minus 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 plus/minus 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 plus/minus 2% and 36 plus/minus 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. (Hypertension. 1996;27[part 1]:382-391.)