PREGLOMERULAR SUDANOPHILIA IN L-NAME HYPERTENSIVE RATS - INVOLVEMENT OF ENDOTHELIN

To characterize alterations of renal vessels occurring during systemic hypertension elicited in rats by 5, 10, and 25 days of treatment by t he nitric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester ( L-NAME) (20 mg/kg daily), preglomerular vasculatures, consisting of ar cuate 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 hype rtensive arcuate arterial branches and interlobular arteries but not o f afferent arterioles had focal deposits of Sudan black-positive lipid droplets. At 25 days, vessel wall thickness increased by 72+/-6% alon g the sudanophilic areas. Immunostaining of sudanophilic lesions with a panel of antibodies unveiled medial cell proliferation, macrophage i nvasion, immunoreactive vascular cell adhesion molecule-1, and low-den sity lipoprotein. The frequency of sudanophilic lesions increased with time to affect 26+/-2% and 36+/-3% of arcuate arterial branches and i nterlobular arteries, respectively, at 25 days. Hypertensive L-NAME-tr eated rats developed glomerular injury probed by albuminuria and glome rular immunostaining for alpha-smooth muscle actin. administration of the nonselective endothelin antagonist bosentan (30 mg/kg daily) blunt ed the development of sudanophilic lesions during L-NAME treatment wit hout affecting arterial hypertension or degree of glomerular injury. T herefore, L-NAME hypertension leads to rapid development of focal, inf lammatory, proliferative, and sudanophilic lesions along preglomerular vessels, suggesting atherosclerosis-like processes. Furthermore, endo thelin is a likely mediator in the development of these lesions.