title: Increased brain angiotensin receptor in rats with chronic high-output heart failure.
abstract: BACKGROUND
  The renin-angiotensin system (RAS) plays a key role in the pathophysiology of chronic heart failure (CHF). In rats, we reported that CHF enhances dipsogenic responses to centrally administered angiotensin I, and central inhibition of the angiotensin-converting enzyme (ACE) prevents cardiac hypertrophy in CHF. This suggests that the brain RAS is activated in CHF. To clarify the mechanism of the central RAS activation in CHF, we examined brain ACE and the angiotensin receptor (AT) among rats with CHF.
  
  
  RESULTS
  We created high-output heart failure in 22 male Sprague-Dawley rats by aortocaval shunt. Four weeks after surgery, we examined ACE mRNA by reverse transcriptase polymerase chain reaction (RT-PCR) and AT by binding autoradiography. ACE mRNA levels were not significantly increased in the subfornical organ (SFO), the hypothalamus, or in the lower brainstem of CHF rats (n = 5) compared with sham-operated rats (SHM) (n = 6). Binding densities for type 1 AT (AT1) in the SFO (P < .05), paraventricular hypothalamic nuclei (P < .05), and solitary tract nuclei (P < .05) were higher in rats with CHF (n = 5) than in SHM rats (n = 6). Thus, in rats with CHF, AT1 expression is increased in brain regions that are closely related to water intake, vasopressin release, and hemodynamic regulation.
  
  
  CONCLUSIONS
  The fact that AT1 expression was upregulated in important brain regions related to body fluid control in CHF rats indicates that the brain is a major site of RAS action in CHF rats and, therefore, a possible target site of ACE-inhibitors in the treatment of CHF.
authors.affiliation: Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Yoshimura
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Kawada
authors.forename: T
authors.initials: T
authors.lastname: Shishido
authors.forename: M
authors.initials: M
authors.lastname: Inagaki
authors.forename: H
authors.initials: H
authors.lastname: Miyano
authors.forename: T
authors.initials: T
authors.lastname: Nakahara
authors.forename: H
authors.initials: H
authors.lastname: Miyashita
authors.forename: H
authors.initials: H
authors.lastname: Takaki
authors.forename: T
authors.initials: T
authors.lastname: Tatewaki
authors.forename: Y
authors.initials: Y
authors.lastname: Yanagiya
authors.forename: M
authors.initials: M
authors.lastname: Sugimachi
authors.forename: K
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000818:Animals; D001345:Autoradiography; D015415:Biomarkers; D001933:Brain Stem / Q000378:metabolism*; D002908:Chronic Disease; D004195:Disease Models, Animal; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006439:Hemodynamics; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D007703:Peptidyl-Dipeptidase A