Inhibition of brain nitric oxide synthesis enhances and prolongs the hypertensive effect of centrally administered interleukin-1β in rats

Abstract

The present study was designed to find out whether brain nitric oxide (NO) influences hemodynamic response to intracerebroventricular (ICV) infusion of interleukin-1 β (IL-1β). Mean arterial blood pressure (MAP) and heart rate (HR) were recorded in seven series of experiments performed on conscious Sprague–Dawley rats receiving during 60 min ICV infusion of: 0.9% NaCl (5 μl/h; series 1), IL-1β (100 ng/h; series 2), NO synthase inhibitor (L-NAME, 1 mg/h; series 3), IL-1β together with L-NAME (series 4), IL-1β together with inactive isomer of NO synthase inhibitor (D-NAME, 1 mg/h; series 5), NO donor (SNAP, 40 μg/h; series 6) and IL-1β together with SNAP (series 7). ICV infusion of saline did not influence MAP while administration of IL-1β as well as IL-1β together with D-NAME elicited a significant, though transient, increase in MAP. In series 4, combined infusion of IL-1β and L-NAME exerted an increase in MAP, which persisted until the end of the experiment and was significantly higher than in series 2 and 5. In series 7, infusion of SNAP together with IL-1β abolished the pressor effect of IL-1β. HR was not significantly altered in any of the experimental series. These results demonstrate that inhibition of NO synthesis in the brain enhances and prolongs the pressor response to IL-1β, whereas concomitant administration of NO donor abolishes the hemodynamic effect of IL-1β. Therefore, we conclude that NO generated in the brain is involved in buffering the pressor response to IL-1β.