(Hypertension. 1998;31:266.)
© 1998 American Heart Association, Inc.
Scientific Contributions |
Nitric Oxide Synthase Activity and Renal Injury in Genetic Hypertension
From the Department of Medicine, Veterans Affairs Medical Center and University of Minnesota Medical School, Minneapolis, Minnesota.
Correspondence to Leopoldo Raij, MD, VA Medical Center, Nephrology/Hypertension Section, III j, 1 Veterans Drive, Minneapolis, MN, 55417. E-mail: raijx001{at}maroon.tc.umn.edu
Nitric oxide (NO) is an endogenous vasodilator synthesized in the endothelium by constitutive NO synthase (cNOS). We have shown that upregulation of cNOS activity in hypertension may contribute to forestalling left ventricular and aortic hypertrophy (Hypertension. 29: 235, 1997). NO has been shown to inhibit growth-related responses affecting vascular smooth muscle, and mesangial cells, as well as reduce production of extracellular matrix in response to injury. Here, we investigated the relationship between renal cNOS activity (conversion of [14C] L-arginine to [14C] L-citrulline) and glomerular (GIS) and tubulointerstitial (TIS) injury scores and urinary protein excretion, indices of renal injury, in age and blood pressure matched spontaneously hypertensive rats (SHR, SBP 220±9 mm Hg) fed 0.5% NaCl diet and Dahl salt-sensitive (DS) rats fed 4% NaCl diet (DS-4%, SBP 228±8 mm Hg) as well as their normotensive counterparts Wistar Kyoto rats fed 0.5% NaCl diet (WKY, 137±3 mm Hg) and DS rats fed 0.5% NaCl diet (DS-0.5%, SBP 135±4 mm Hg). In SHR, renal medullary cNOS activity was 89% higher than in WKY (8.91±0.98 vs 4.71±0.37 nmol/min/g protein, P<0.05) whereas, in hypertensive DS-4% rats cNOS activity was 43% lower than in DS-0.5% rats (1.98±0.16 vs 3.48±0.29 nmol/min/g protein, P<0.05). Renal cortical cNOS was lower than in medulla but similar in all groups; inducible NOS activity was not detected. Despite hypertension of similar severity and duration, hypertensive DS-4% developed 9 fold more GIS (190±42 vs 21±11), 20 fold more TIS (4.0±0.7 vs 0.2±0.3), and 5 fold more proteinuria (54±11 vs 8.5±3.0 mg/day), all P<0.05. The current studies, in conjunction with our recent studies in heart and aorta, strongly suggest that in hypertension, increased cNOS activity may provide a protective homeostatic role in all the end-organs that are targets of hypertensive injury.
Key Words: nitric oxide synthase • rats, inbred, SHR • rats, Dahl • hypertension • glomerular injury • renal tubulo-interstitial injury • salt sensitivity
Abbreviations: ACh = acetylcholine • cNOS = constitutive nitric oxide synthase • DS = Dahl salt-sensitive rat • DR = Dahl salt-resistant rat • GIS = glomerular injury score • LNAME = NG-nitro-L-arginine methyl-ester • NO = nitric oxide • NOS = nitric oxide synthase • RMBF = renal medullary blood flow • SBP = systolic blood pressure • SHR = spontaneously hypertensive rats • TIS = tubulointerstitial injury score • UproV = urinary protein excretion per day • PAS = periodic acid Schiff • HE = hematoxylin and eosin • WKY = Wistar-Kyoto rats
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