NITRIC-OXIDE SYNTHASE ACTIVITY AND RENAL INJURY IN GENETIC-HYPERTENSION

Nitric oxide (NO) is an endogenous vasodilator synthesized in the endo thelium by constitutive NO synthase (cNOS). We have shown that upregul ation 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 vascu lar smooth muscle, and mesangial cells, as well as reduce production o f extracellular matrix in response to injury. Here, we investigated th e relationship between renal cNOS activity (conversion of [C-14] L-arg inine to [C-14] L-citrulline) and glomerular (GIS) and tubulointerstit ial (TIS) injury scores and urinary protein excretion, indices of rena l injury, in age and blood pressure matched spontaneously hypertensive rats (SHR, SBP 220+/-9 mm Hg) fed 0.5% NaCl diet and Dahl salt-sensit ive (DS) rats fed 4% NaCl diet (DS-4%, SBP 228+/-8 mm Hg) as well as t heir normotensive counterparts Wistar Kyoto rats fed 0.5% NaCl diet (W KY, 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 c ortical cNOS was lower than in medulla but similar in all groups; indu cible NOS activity was not detected. Despite hypertension of similar s everity and duration, hypertensive DS-4% developed 9 fold more GIS (19 0+/-42 vs 21+/-11), 20 fold more TIS (4.0+/-0.7 vs 0.2+/-0.3), and 5 f old more proteinuria (54+/-11 vs 8.5+/-3.0 mg/day), all P<0.05. The cu rrent studies, in conjunction with our recent studies in heart and aor ta, 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.