PMID- 15066903
OWN - NLM
STAT- MEDLINE
DCOM- 20041227
LR  - 20181113
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 142
IP  - 2
DP  - 2004 May
TI  - Correlation between brain bradykinin receptor binding sites and cardiovascular 
      function in young and adult spontaneously hypertensive rats.
PG  - 285-96
AB  - Intracerebroventricular (i.c.v.) effects of bradykinin (BK) B(1) and B(2) 
      receptor agonists and antagonists were assessed on mean arterial blood pressure 
      (MAP) and heart rate (HR) in awake unrestrained spontaneously hypertensive rats 
      (SHR, aged of 8 and 16 weeks) and age-matched Wistar Kyoto rats (WKY). 
      Quantitative in vitro autoradiographic studies were also performed on the brain 
      of both strains with specific radioligands for B(2) receptors [(125)I]HPP-Hoe 140 
      and B(1) receptors [(125)I]HPP-des-Arg(10) and Hoe140. MAP increased linearly 
      with doses of BK (81-8100 pmol) and the amplitudes were significantly greater in 
      SHR, particularly at 16 weeks. While BK evoked a negative linear trend on HR 
      (bradycardia) in WKY, a positive one (tachycardia) was observed in adult SHR. In 
      both strains, BK-induced pressor response was blocked by equimolar doses of B(2) 
      receptor antagonist, D-Arg-[Hyp(3), Thi(5), D-Tic(7), Oic(8)]-BK (Hoe 140), but 
      not by B(1) receptor antagonist, AcLys[D-betaNal(7), Ile(8)]des-Arg(9)-BK 
      (R-715). B(1) receptor agonists (Sar-[D-Phe(8)]-des-Arg(9)-BK, des-Arg(9)-BK, 
      des-Arg(10)-Kallidin) and antagonist (R-715 alone or with Hoe 140) had no or 
      marginal effect on MAP and HR at doses up to 8100 pmol in SHR and WKY. Higher 
      densities of specific [(125)I]HPP-Hoe 140 labelling were found in discrete brain 
      areas of SHR, especially in regions associated with cardiovascular function. Low 
      levels of [(125)I]HPP-[des-Arg(10)]-Hoe140 binding sites were seen in WKY and 
      SHR, yet densities were significantly greater in midbrain and cortical regions of 
      SHR aged of 16 weeks. Contrary to SHR, ageing caused a downregulation of B(2) and 
      B(1) receptor binding sites in specific brain nuclei in WKY. It is concluded that 
      the hypersensitivity of the pressor response to i.c.v. BK in SHR occurs during 
      both the early and established phases of hypertension in parallel with the 
      enhancement of B(2) receptor binding sites in various cardiovascular brain 
      centres. In contrast, brain B(1) receptors do not seem to participate in the 
      central pressor effects of kinins nor in the maintenance of hypertension in SHR.
FAU - Cloutier, Frank
AU  - Cloutier F
AD  - Department of Physiology, Faculty of Medicine, Universite de Montreal, C.P. 6128, 
      Succursale Centre-ville, Montreal, Quebec, Canada H3C 3J7.
FAU - Ongali, Brice
AU  - Ongali B
FAU - Campos, Maria M
AU  - Campos MM
FAU - Thibault, Gaetan
AU  - Thibault G
FAU - Neugebauer, Witold
AU  - Neugebauer W
FAU - Couture, Rejean
AU  - Couture R
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040405
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Bradykinin Receptor Antagonists)
RN  - 0 (Receptors, Bradykinin)
RN  - 7PG89G35Q7 (icatibant)
RN  - S8TIM42R2W (Bradykinin)
SB  - IM
MH  - Aging/drug effects/*metabolism
MH  - Animals
MH  - Binding Sites/drug effects/physiology
MH  - Blood Pressure/drug effects/*physiology
MH  - Bradykinin/*analogs & derivatives/metabolism/pharmacology
MH  - Bradykinin Receptor Antagonists
MH  - Brain/drug effects/*metabolism
MH  - Cardiovascular System/drug effects/metabolism
MH  - Heart Rate/drug effects/*physiology
MH  - Hypertension/*metabolism
MH  - Male
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Receptors, Bradykinin/agonists/*metabolism
PMC - PMC1574947
EDAT- 2004/04/07 05:00
MHDA- 2004/12/28 09:00
PMCR- 2005/05/01
CRDT- 2004/04/07 05:00
PHST- 2004/04/07 05:00 [pubmed]
PHST- 2004/12/28 09:00 [medline]
PHST- 2004/04/07 05:00 [entrez]
PHST- 2005/05/01 00:00 [pmc-release]
AID - 0705759 [pii]
AID - 10.1038/sj.bjp.0705759 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2004 May;142(2):285-96. doi: 10.1038/sj.bjp.0705759. Epub 2004 
      Apr 5.