Abstract
We investigated whether changes in nitric oxide (NO) release might be responsible for the modulation by glucocorticoids of the pressor response to i.p. injection of interleukin-1β (IL-1β) in freely moving rats. In such rats, IL-1β (10 μg/kg) induced a biphasic pressor response, with a rise in the plasma concentration of NOx (NO2− andNO3− : metabolites of NO) during the second phase. Systemic pretreatment with an exogenous glucocorticoid, dexamethasone (0.5 mg/kg), enhanced the second phase of the pressor response and completely suppressed the increase in plasma NOx. Treatment withNω-nitro-l-arginine methyl ester (l-NAME, a nonspecific NO synthase inhibitor), enhanced the pressor response while attenuating the increase in plasma NOx. After bilateral adrenalectomy, IL-1β induced a smaller pressor response, but a larger increase in plasma NOx; dexamethasone reversed these changes. Our results suggest that endogenous NO moderates the pressor response to IL-1β in freely moving rats, and that glucocorticoids enhance the IL-1β-induced pressor response at least in part by reducing endogenous NO release.
Footnotes
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Send reprint requests to: Tatsuo Watanabe, M.D., Ph.D., Department of Physiology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755 Japan. E-mail: tatsuo{at}po.cc.yamaguchi-u.ac.jp
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↵1 This work was partly supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan.
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↵2 Current address: Department of Critical Care and Emergency Medicine, Yamaguchi University School of Medicine, Ube, Yamaguchi 755, Japan.
- Abbreviations:
- IL-1
- interleukin-1
- DEX
- dexamethasone
- ADX
- adrenalectomized
- NO
- nitric oxide
- NO2−
- nitrite
- NO3−
- nitrate
- NOx
- NO2− and NO3−
- L-NAME
- Nω-nitro-l-arginine methyl ester
- LPS
- lipopolysaccharide
- cNOS
- constitutive NO synthase
- iNOS
- inducible NO synthase
- Received December 30, 1997.
- Accepted October 21, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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