Brain nuclear factor-kappa B activation contributes to neurohumoral excitation in angiotensin II-induced hypertension
Open Access
- 25 February 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in Cardiovascular Research
- Vol. 82 (3), 503-512
- https://doi.org/10.1093/cvr/cvp073
Abstract
Angiotensin II (ANG II)-induced inflammatory and oxidative stress responses contribute to the pathogenesis of hypertension. In this study, we determined whether nuclear factor-kappa B (NF-κB) activation in the hypothalamic paraventricular nucleus (PVN) increases oxidative stress and contributes to the ANG II-induced hypertensive response. Rats were infused intravenously with ANG II (10 ng/kg per min) or saline for 4 weeks. These rats received either vehicle or losartan (LOS, 20 µg/h), an angiotensin II type 1 receptor (AT1-R) antagonist; pyrrolidine dithiocarbamate (PDTC, 5 µg/h), a NF-κB inhibitor; tempol (TEMP, 80 µg/h), a superoxide scavenger; LOS (20 µg/h), and PDTC (5 µg/h); or TEMP (80 µg/h) and PDTC (5 µg/h), given intracerebroventricularly (ICV) via osmotic minipump. ANG II infusion resulted in increased mean arterial pressure, renal sympathetic nerve activity, plasma proinflammatory cytokines (PIC), norepinephrine, and aldosterone. These rats also had higher levels of Fra-LI (an indicator of chronic neuronal activation), PIC, phosphorylated IKKβ, NF-κB subunits, AT1-R, superoxide, and gp91phox (a subunit of NADP(H) oxidase) and lower levels of IκBα in the PVN than control animals. ICV treatment with LOS, PDTC, or TEMP attenuated these changes, and combined treatment with ICV LOS and PDTC, or ICV TEMP and PDTC prevented these ANG II-induced hypertensive responses. These findings suggest that an ANG II-induced increase in the brain renin–angiotensin system activates NF-κB in the PVN and contributes to sympathoexcitation in hypertension. The increased superoxide in the PVN contributes to NF-κB activation and neurohumoral excitation in hypertension.Keywords
This publication has 36 references indexed in Scilit:
- Sympathoexcitation by Oxidative Stress in the Brain Mediates Arterial Pressure Elevation in Salt-Sensitive HypertensionHypertension, 2007
- TNF-α blockade decreases oxidative stress in the paraventricular nucleus and attenuates sympathoexcitation in heart failure ratsAmerican Journal of Physiology-Heart and Circulatory Physiology, 2007
- Novel Effect of Mineralocorticoid Receptor Antagonism to Reduce Proinflammatory Cytokines and Hypothalamic Activation in Rats With Ischemia-Induced Heart FailureCirculation Research, 2006
- An emerging role for inflammatory cytokines in hypertensionAmerican Journal of Physiology-Heart and Circulatory Physiology, 2006
- Acute Tumor Necrosis Factor Alpha Signaling via NADPH Oxidase in Microvascular Endothelial Cells: Role of p47phox Phosphorylation and Binding to TRAF4Molecular and Cellular Biology, 2005
- The IKKβ Subunit of IκB Kinase (IKK) is Essential for Nuclear Factor κB Activation and Prevention of ApoptosisThe Journal of Experimental Medicine, 1999
- Endogenous ANG II supports lumbar sympathetic activity in conscious sodium-deprived rats: role of area postremaAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1998
- Changes of Plasma Endothelin and Growth Factor Levels, and of Left Ventricular Mass, After Chronic AT1-Receptor Blockade in Human HypertensionAmerican Journal of Hypertension, 1998
- Regulation of Vascular Type 1 Angiotensin Receptors by CytokinesHypertension, 1997
- Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone.JCI Insight, 1996