Vol. 289, Issue 1, 24-30, April 1999

Glucocorticoid Enhances Interleukin-1-Induced Pressor Response in Freely Moving Rats Through Its Effect on Nitric Oxide Release¹

Tatsuo Watanabe, Yoshiyuki Sakata, Takashi Fujioka, Daikai Sadamitsu² and Tsuyoshi Maekawa²

Department of Physiology and Department of Critical Care and Emergency Medicine, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan

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-1 (IL-1) in freely moving rats. In such rats, IL-1 (10 µg/kg) induced a biphasic pressor response, with a rise in the plasma concentration of NOx (NO2 and NO3: 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 with N-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-1 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-1 in freely moving rats, and that glucocorticoids enhance the IL-1-induced pressor response at least in part by reducing endogenous NO release.