(Hypertension. 1997;30:1479-1486.)
© 1997 American Heart Association, Inc.
Articles |
Regional Renal Nitric Oxide Release in Stroke-Prone Spontaneously Hypertensive Rats
From the Departments of Pediatrics (A.Z.), Pathology (P.N.C.), and Pharmacology (C.T.S.), New York Medical College, Valhalla, NY, and the Department of Medicine (G.A.Z.), Veterans Administration Hospital, Bronx, NY.
Correspondence to Andrea Zuckerman, MD, Department of Pediatrics, New York Medical College, Valhalla, NY 10595.
Abstract Diminished nitric oxide (NO) production has
been implicated in the pathogenesis of salt-sensitive hypertension. We
questioned whether such a defect is responsible for the malignant
hypertension and nephrosclerosis in stroke-prone
spontaneously hypertensive rats (SHRSP) fed a high-salt/stroke-prone
diet (S) versus a regular diet (R). NO release from 30-minute incubates
of cortex and outer and inner medulla were studied in SHRSP at 10, 12,
and 16 weeks of age on the S diet versus R diet. SHRSP-S (n=16)
exhibited a marked age-dependent increase in NO release, especially in
the cortex. Increases were only modest in SHRSP-R (n=21). At 16 weeks,
cortical NO was 93±25 versus 6±1 pmol/mg tissue in SHRSP-S versus
SHRSP-R (P<.001). Immunohistochemical staining
increased mostly for neuronal, slightly for
endothelial, and negligibly for inducible isoforms of
NO synthase and was predominantly in the cortex of SHRSP-S versus
SHRSP-R. Despite similar hypertension in SHRSP-S versus SHRSP-R (mean
arterial pressure, 174±7 versus 177±2 mm Hg),
malignant nephrosclerosis was seen only in SHRSP-S,
affecting 22±6% of glomeruli and 23±4 vessels per 100 glomeruli by
16 weeks. N
-nitro-L-arginine
(15 mg/kg per day) in SHRSP-S (n=6) abrogated the increase in cortical
NO but further augmented the hypertension and accelerated lesion
development. Wistar-Kyoto rats at 16 weeks on the R diet (n=8) had NO
levels similar to those of SHRSP-R, showed increased cortical NO to
only 28±10 pmol/mg on the S diet (n=9) (P<.05 versus
SHRSP-S), but remained normotensive and lesion-free. We conclude that
hypertension and lesion development in SHRSP are not due to deficient
renal NO. Accelerated onset of malignant
nephrosclerosis by NO synthase inhibition suggests that
NO is protective in these animals, mitigating the effects of
hypertension and S diet on renal pathology.
Key Words: rats, inbred SHR • rats, Wistar-Kyoto • malignant nephrosclerosis • sodium • N-nitro-L-arginine • nitric oxide synthase
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