Abstract
Our previous work indicated that subfornical organ (SFO) is an important brain sensor mediating the effects of blood‐borne pro‐inflammatory cytokines (PIC) on autonomic and cardiovascular function. However, the mechanisms by which SFO mediates these central effects of circulating PIC remain unclear. In this study, we examine whether the brain renin‐angiotensin system (RAS) in the SFO contributes to the excitatory effects of PIC on blood pressure (BP, mmHg), heart rate (HR, bpm) and renal sympathetic nerve activity (RSNA, %). In urethane anesthetized SD rats (n=6), microinjection of interleukin‐1β (IL‐1β, 20 ng) into the SFO significantly (*p<0.01) elevated BP (19.3 ± 2.0*), HR (70 ± 7*) and RSNA (84.6 ± 4.2*). Pretreatment of SFO with the angiotensin II type 1 receptor (AT1‐R) blocker losartan (5 μg, n=6) or the angiotensin converting enzyme inhibitor captopril (5 μg, n=6) significantly reduced IL‐1β induced BP, HR and RSNA responses. SFO microinjection of tumor necrosis factor‐α (20 ng, n=4) elicited similar increases in BP, HR and RSNA that were also significantly attenuated by SFO pretreatment with losartan or captopril. AT1‐R mRNA expression in the SFO was markedly increased (from 1.03 ± 0.11 to 2.05 ± 0.24*) 4 hr after intravenous injection of IL‐1β (1 μg/kg). These data suggest that circulating PIC elicit hemodynamic and sympathetic responses at least in part by upregulating RAS activity in the SFO.
Published Version
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