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<.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 omega-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.

• Authors: A Zuckerman, P N Chander, G A Zeballos, C T Stier Jr
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 30 Issue 6 Pg. 1479-86 (Dec 1997) ISSN: 0194-911X [Print] United States
• PMID: 9403570 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Sodium, Dietary
• Nitroarginine
• Nitric Oxide
• Nitric Oxide Synthase

Topics

• Aging (metabolism)
• Animals
• Blood Pressure
• Cerebrovascular Disorders
• Hypertension (metabolism, pathology, physiopathology)
• Kidney Cortex (drug effects, metabolism, pathology)
• Kidney Glomerulus (pathology)
• Kidney Medulla (drug effects, metabolism, pathology)
• Male
• Nitric Oxide (biosynthesis)
• Nitric Oxide Synthase (metabolism)
• Nitroarginine (pharmacology)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Renal Circulation
• Sodium, Dietary