Proinflammatory cytokines upregulate sympathoexcitatory mechanisms in the subfornical organ of the rat

Hypertension
Shun-Guang WeiRobert B Felder

Abstract

Our previous work indicated that the subfornical organ (SFO) is an important brain sensor of blood-borne proinflammatory cytokines, mediating their central effects on autonomic and cardiovascular function. However, the mechanisms by which SFO mediates the central effects of circulating proinflammatory cytokines remain unclear. We hypothesized that proinflammatory cytokines act within the SFO to upregulate the expression of excitatory and inflammatory mediators that drive sympathetic nerve activity. In urethane-anesthetized Sprague-Dawley rats, direct microinjection of tumor necrosis factor (TNF)-α (25 ng) or interleukin (IL)-1β (25 ng) into SFO increased mean blood pressure, heart rate, and renal sympathetic nerve activity within 15 to 20 minutes, mimicking the response to systemically administered proinflammatory cytokines. Pretreatment of SFO with microinjections of the angiotensin II type-1 receptor blocker losartan (1 μg), angiotensin-converting enzyme inhibitor captopril (1 μg) or cyclooxygenase-2 inhibitor NS-398 (2 μg) attenuated those responses. Four hours after the SFO microinjection of TNF-α (25 ng) or IL-1β (25 ng), mRNA for angiotensin-converting enzyme, angiotensin II type-1 receptor, TNF-α and the p55 TNF-α recept...Continue Reading

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