Centrally administered interleukin‐1 beta sensitizes to the central pressor action of angiotensin II

Abstract

Several lines of evidence indicate that both peripherally and centrally released cytokines might exert significant effects on the cardiovascular system. The goal of the present study was to find out whether brain angiotensin II (Ang II) is involved in hemodynamic response to intracerebroventricular (ICV) infusion of interleukin-1 beta (IL-1β). Mean arterial blood pressure (MABP) and heart rate (HR) were recorded in 6 series of experiments performed on conscious Sprague Dawley rats. ICV infusion of 0.9% sterile NaCl [5μL/hr – control] did not influence MABP, whereas, ICV infusion of IL-1β [100ng/5μL/hr] resulted in significant, however, transient increase in MABP. ICV infusion of IL-1β together with angiotensin type 1 (AT1) receptor antagonist (losartan), [IL-1β 100ng + losartan 10μg/hr] as well as ICV infusion of losartan alone [10μg/hr] failed to evoke any changes in MABP. ICV infusion of Ang II [5ng/15sec.] resulted in significant increase in MABP in the rats, which were ICV pretreated with IL-1β [100ng/5μL/hr]. In contrast the same dose of Ang II failed to influence MABP in the rats ICV pretreated with 0.9% sterile NaCl [5μL/hr – control]. The results of the present study provide evidence that brain AT1 receptors are involved in the pressor response to centrally administered IL-1β. Furthermore, IL-1β through its action in the brain increases sensitivity to central pressor action Ang II. The study was supported by the Medical University of Warsaw and by a grant from the Polish Ministry of Education and Science. Losartan was a generous gift from Merck.