PMID- 16304626
OWN - NLM
STAT- MEDLINE
DCOM- 20060307
LR  - 20131121
IS  - 0021-9967 (Print)
IS  - 0021-9967 (Linking)
VI  - 493
IP  - 4
DP  - 2005 Dec 26
TI  - Effects of intracerebroventricular losartan on angiotensin II-mediated pressor 
      responses and c-fos expression in near-term ovine fetus.
PG  - 571-9
AB  - The renin-angiotensin system plays an important role in cardiovascular control. 
      Intracerebroventricular (i.c.v.) angiotensin (ANG) II causes a reliable pressor 
      response in the fetus at 90% gestation. To determine the roles of brain AT1 and 
      AT2 receptors in this response, the effects of the central AT1 and AT2 receptor 
      antagonists losartan and PD123319 were investigated in chronically prepared 
      near-term ovine fetuses. Losartan at 0.5 mg/kg (i.c.v.) abolished central ANG 
      II-induced pressor responses. High-dose losartan (5 mg/kg, i.c.v.) showed a 
      potentiation of the pressor response to i.c.v. ANG II, accompanied by 
      bradycardia. Associated with the pressor responses, c-fos expression in the 
      cardiovascular controlling areas was significantly different between the low and 
      high doses of losartan. These areas included the subfornical organ, median 
      preoptic nucleus, organum vasculosum of the lamina terminalis, and 
      paraventricular nuclei in the forebrain, and the tractus solitarius nuclei, 
      lateral parabrachial nuclei in the hindbrain. Low-dose losartan markedly reduced 
      c-fos in these areas after i.c.v. ANG II, while the high-dose losartan together 
      with ANG II elicited a much stronger FOS-immunoreactivity in these areas than 
      that induced by i.c.v. ANG II alone. This is a novel finding, that c-fos 
      expression in the brain can be both activated and inhibited under the same 
      condition. Central ANG II-induced fetal pressor responses were not altered by 
      PD123319 (0.8 mg/kg). These results indicate that i.c.v. losartan at a high and a 
      low dose has strikingly different effects on central ANG II-induced pressor 
      responses in fetuses at late gestation, and that the AT1 mechanism plays an 
      important role in fetal cardiovascular regulation.
CI  - Copyright (c) 2005 Wiley-Liss, Inc.
FAU - Shi, Lijun
AU  - Shi L
AD  - Research & Education Institute, Harbor-University of California, Los Angeles 
      Medical Center, Torrance, California 90501, USA.
FAU - Mao, Caiping
AU  - Mao C
FAU - Thornton, Simon N
AU  - Thornton SN
FAU - Sun, Wanping
AU  - Sun W
FAU - Wu, Jiawei
AU  - Wu J
FAU - Yao, Jiaming
AU  - Yao J
FAU - Xu, Zhice
AU  - Xu Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Comp Neurol
JT  - The Journal of comparative neurology
JID - 0406041
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 11128-99-7 (Angiotensin II)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - Analysis of Variance
MH  - Angiotensin II/administration & dosage/*drug effects/metabolism
MH  - Angiotensin II Type 1 Receptor Blockers/*administration & dosage
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Cardiovascular System/drug effects/embryology/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Fetus/drug effects
MH  - Genes, fos/*drug effects/physiology
MH  - Gestational Age
MH  - Homeostasis/drug effects/physiology
MH  - Injections, Intraventricular
MH  - Losartan/*administration & dosage
MH  - Pregnancy
MH  - Prosencephalon/*drug effects/embryology/metabolism
MH  - Sheep
MH  - Statistics, Nonparametric
EDAT- 2005/11/24 09:00
MHDA- 2006/03/08 09:00
CRDT- 2005/11/24 09:00
PHST- 2005/11/24 09:00 [pubmed]
PHST- 2006/03/08 09:00 [medline]
PHST- 2005/11/24 09:00 [entrez]
AID - 10.1002/cne.20802 [doi]
PST - ppublish
SO  - J Comp Neurol. 2005 Dec 26;493(4):571-9. doi: 10.1002/cne.20802.