title: Brain nuclear factor-kappa B activation contributes to neurohumoral excitation in angiotensin II-induced hypertension.
abstract: OBJECTIVE
  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-kappaB) activation in the hypothalamic paraventricular nucleus (PVN) increases oxidative stress and contributes to the ANG II-induced hypertensive response.
  
  
  RESULTS
  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 microg/h), an angiotensin II type 1 receptor (AT1-R) antagonist; pyrrolidine dithiocarbamate (PDTC, 5 microg/h), a NF-kappaB inhibitor; tempol (TEMP, 80 microg/h), a superoxide scavenger; LOS (20 microg/h), and PDTC (5 microg/h); or TEMP (80 microg/h) and PDTC (5 microg/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 IKKbeta, NF-kappaB subunits, AT1-R, superoxide, and gp91phox (a subunit of NADP(H) oxidase) and lower levels of IkappaBalpha 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.
  
  
  CONCLUSIONS
  These findings suggest that an ANG II-induced increase in the brain renin-angiotensin system activates NF-kappaB in the PVN and contributes to sympathoexcitation in hypertension. The increased superoxide in the PVN contributes to NF-kappaB activation and neurohumoral excitation in hypertension.
authors.affiliation: Shantou University Medical College, Shantou 515041, People's Republic of China. ymkang@lsu.edu
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Kang
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Zheng
authors.forename: Carrie
authors.initials: C
authors.lastname: Elks
authors.forename: Srinivas
authors.initials: S
authors.lastname: Sriramula
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Yang
authors.forename: Joseph
authors.initials: J
authors.lastname: Francis
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D000975:Antioxidants; D001794:Blood Pressure; D003497:Cyclic N-Oxides; D016207:Cytokines / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013859:Thiocarbamates
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D003497:Cyclic N-Oxides; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D013113:Spin Labels; D013859:Thiocarbamates; D013481:Superoxides; D000804:Angiotensin II; C066229:prolinedithiocarbamate; D011392:Proline; D019255:NADPH Oxidases; C001803:tempol