Regional Renal Nitric Oxide Release in Stroke-Prone Spontaneously Hypertensive Rats

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 N ω -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