Cross-talk between cytokines and renin-angiotensin in hypothalamic paraventricular nucleus in heart failure: role of nuclear factor- B

Abstract

These findings indicate that NF-kappaB mediates the cross-talk between RAS and PIC in the PVN in HF, and that superoxide stimulates more NF-kappaB in the PVN and contributes to neurohumoral excitation.

TNF-.ALPHA. in Hypothalamic Paraventricular Nucleus Contributes to Sympathoexcitation in Heart Failure by Modulating AT1 Receptor and Neurotransmitters

“…Recent studies also suggest that proinflammatory cytokines and the renin-angiotensin system (RAS) can contribute to these changes (Kang et al 2008a(Kang et al , 2008b(Kang et al , 2009a(Kang et al , 2009b. Our laboratory and others have reported that cytokine blockade in the brain decreases components of the RAS (Kang et al 2008b, Guggilam et al 2008 and that RAS blockade attenuates production of proinflammatory cytokines (Kang et al 2008a(Kang et al , 2009b.…”

“…Recent studies suggest that proinflammatory cytokines are upregulated in the PVN, thereby leading to sympathoexcitation in HF (Kang et al 2008a(Kang et al , 2008b. TNF-α , IL-1β , and IL-6 can all activate the hypothalamic-pituitary-adrenal (HPA) axis (Turnbull and Rivier 1999;Dunn 2000) and contribute to increased sympathetic nerve activity .…”

“…Recent studies also suggest that proinflammatory cytokines and the renin-angiotensin system (RAS) can contribute to these changes (Kang et al 2008a(Kang et al , 2008b(Kang et al , 2009a(Kang et al , 2009b. Our laboratory and others have reported that cytokine blockade in the brain decreases components of the RAS (Kang et al 2008b, Guggilam et al 2008 and that RAS blockade attenuates production of proinflammatory cytokines (Kang et al 2008a(Kang et al , 2009b. We inhibited cytokine synthesis in the brain with centrally infused pentoxifylline (PTX) and found that lowering hypothalamic levels of TNF-α and IL-1β without changing plasma cytokine levels is associated with reductions in brain renin, ACE, and AT1-R, strongly suggests that proinflammatory cytokines are intrinsically involved in regulating brain RAS, and thus sympathetic nerve activity and extracellular fluid volume, in rats with HF.…”

“…We inhibited cytokine synthesis in the brain with centrally infused pentoxifylline (PTX) and found that lowering hypothalamic levels of TNF-α and IL-1β without changing plasma cytokine levels is associated with reductions in brain renin, ACE, and AT1-R, strongly suggests that proinflammatory cytokines are intrinsically involved in regulating brain RAS, and thus sympathetic nerve activity and extracellular fluid volume, in rats with HF. Animals were intracerebroventricularly (ICV) treated with the angiotensin type 1 receptor (AT1-R) antagonist losartan and we found that plasma levels of NE, angiotensin II and proinflammatory cytokines were reduced (Guggilam et al 2008;Kang et al 2008aKang et al , 2008bKang et al , 2009a. However, it is unknown whether proinflammatory cytokines in the PVN alter angiotensin type 1 receptor (AT1-R) within the PVN to modulate neurotransmitters and contribute to sympathoexcitation in HF.…”

Efeito anti-inflamatório do treinamento físico na insuficiência cardíaca: papel do TNF-α e da IL-10

“…Besides the changes in plasma levels, a recent study 27 showed positive correlations between TNF-α levels in the cardiac myocyte and in the hypothalamic paraventricular nucleus in rats with HF. In addition, these changes were related to a higher neurohumoral excitation in the brain cardiovascular region 28 and greater activation of the renin-angiotensin system 29 , suggesting a possible interaction between these systems (renin-angiotensin system and immune system) which may modulate changes such as sodium and water retention and the cardiac remodeling process in rats with HF.…”