Renal medullary nitric oxide deficit of Dahl S rats enhances hypertensive actions of angiotensin II

Mátyás Szentiványi, Ai Ping Zou, David L. Mattson, Paulo Soares, Carol Moreno, Richard J. Roman, Allen W. Cowley

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Studies were designed to examine the hypothesis that the renal medulla of Dahl salt-sensitive (Dahl S) rats has a reduced capacity to generate nitric oxide (NO), which diminishes the ability to buffer against the chronic hypertensive effects of small elevations of circulating ANG II. NO synthase (NOS) activity in the outer medulla of Dahl S rats (arginine-citrulline conversion assay) was significantly reduced. This decrease in NOS activity was associated with the downregulation of protein expression of NOS I, NOS II, and NOS III isoforms in this region as determined by Western blot analysis. In anesthetized Dahl S rats, we observed that a low subpressor intravenous infusion of ANG II (5 ng·kg-1·min-1) did not increase the concentration of NO in the renal medulla as measured by a microdialysis with oxyhemoglobin trapping technique. In contrast, ANG II produced a 38% increase in the concentration of NO (87 ± 8 to 117 ± 8 nmol/1) in the outer medulla of Brown-Norway (BN) rats. The same intravenous dose of ANG II reduced renal medullary blood flow as determined by laser-Doppler flowmetry in Dahl S, but not in BN rats. A 7-day intravenous ANG II infusion at a dose of 3 ng·kg-1·min-1 did not change mean arterial pressure (MAP) in the BN rats but increased MAP in Dahl S rats from 120 ± 2 to 138 ± 2 mmHg (P < 0.05). ANG II failed to increase MAP after NO substrate was provided by infusion of L-arginine (300 μg·kg-1·min-1) into the renal medulla of Dahl S rats. Intravenous infusion of L-arginine at the same dose had no effect on the ANG II-induced hypertension. These results indicate that an impaired NO counterregulatory system in the outer medulla of Dahl S rats makes them more susceptible to the hypertensive actions of small elevations of ANG II.

Original languageEnglish (US)
Pages (from-to)R266-R272
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume283
Issue number1 52-1
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Brown-Norway rats
  • Nitric oxide synthase
  • Renal medullary blood flow

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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