Inflammatory cytokines in paraventricular nucleus modulate sympathetic activity and cardiac sympathetic afferent reflex in rats

Abstract

TNF-α or IL-1β in the PVN increases blood pressure and sympathetic outflow and enhances the CSAR, which is partially dependent on the AT(1) receptors, while IL-4 or IL-13 in the PVN only increases blood pressure. There is a synergetic effect of Ang II with TNF-α or IL-1β on blood pressure, sympathetic activity and CSAR.

Activation of the (pro)renin receptor in the paraventricular nucleus increases sympathetic outflow in anesthetized rats

“…Activation of these PVN neurons can lead to sympathetic discharge (20,45). Multiple factors affect sympathetic outflow such as sodium, ANG II, glutamate, cytokines, oxidative stress, and nitric oxide (NO) (11,12,34,41,47). Previous studies have demonstrated that brain PRR activation can increase the production of inflammatory cytokines, oxidative stress, and ANG II (32,37,46).…”

Novel mechanism within the paraventricular nucleus reduces both blood pressure and hypothalamic pituitary-adrenal axis responses to acute stress

“…While these effects of MIF have not been demonstrated in the PVN, there is a possibility that increasing MIF levels in the PVN by viral vector-mediated transduction affected stress responses by inhibiting glucocorticoid receptor function. However, such an effect would likely lead to exaggerated as opposed to diminished stress responses by abolishing glucocorticoid-mediated negative feedback on corticotrophin-releasing hormone production in the PVN or by increasing the level of proinflammatory cytokines that also exert pressor effects in the PVN (53). Thus the attenuated blood pressure increases during and after restraint stress are unlikely to be caused by modulation of glucocorticoid signaling.…”

Relevance of Immune-Sympathetic Nervous System Interplay for the Development of Hypertension

“…Cox-2 catalyzes the production of prostaglandin E2 which enters the brain and stimulates paraventricular nucleus neurons (PVN) which, in turn, regulate adrenocorticotropic hormone release and increase sympathetic drive (Felder et al 2009;Felder 2010). Further, direct microinjection of TNF-α and IL-1β to PVN increases blood pressure and sympathetic outflow and enhances the cardiac sympathetic afferent reflex (Shi et al 2011). Intracerebroventricular administration of IL-10 decreases TNF-α, IL-1α, prostaglandin E2, and Cox-2 levels in the PVN and attenuates sympathoexcitation (Yu et al 2007).…”

“…Intracerebroventricular administration of IL-10 decreases TNF-α, IL-1α, prostaglandin E2, and Cox-2 levels in the PVN and attenuates sympathoexcitation (Yu et al 2007). Chronic angiotensin II-induced hypertension is associated with increased expression of inflammatory cytokines and microglial activation in PVN (Shi et al 2011;Colombari et al 2010). Minocycline, an antibiotic that can cross the blood-brain barrier, inhibits microglial activation, attenuates angiotensin II-induced high blood pressure, decreases the amount of PVN inflammatory cytokines, and mitigates cardiac hypertrophy (Shi et al 2011).…”

“…Chronic angiotensin II-induced hypertension is associated with increased expression of inflammatory cytokines and microglial activation in PVN (Shi et al 2011;Colombari et al 2010). Minocycline, an antibiotic that can cross the blood-brain barrier, inhibits microglial activation, attenuates angiotensin II-induced high blood pressure, decreases the amount of PVN inflammatory cytokines, and mitigates cardiac hypertrophy (Shi et al 2011). Most likely, the subfornical organ, a forebrain circumventricular organ that lacks a blood-brain barrier, plays a major role and is a predominant site in the brain at which circulating proinflammatory cytokines act to elicit cardiovascular and sympathetic responses.…”