PMID- 11339503
OWN - NLM
STAT- MEDLINE
DCOM- 20010913
LR  - 20141120
IS  - 1023-3830 (Print)
IS  - 1023-3830 (Linking)
VI  - 50
IP  - 3
DP  - 2001 Mar
TI  - Bradykinin receptor antagonists type 2 attenuate the inflammatory changes in 
      peptidoglycan-induced acute arthritis in the Lewis rat.
PG  - 149-55
AB  - OBJECTIVE AND DESIGN: We studied the ability of bradykinin (BK) receptor 
      antagonists type 1 and 2 (B1-RA, B2-RA) to prevent acute inflammation. MATERIAL: 
      A peptidoglycan-polysaccharide (PG-APS)-induced model of arthritis in the Lewis 
      rat was analyzed. TREATMENT: Four groups of animals were studied for 5 days. 
      Treatment was administered subcutaneously (s.c.) 1 mg/kg every 12 h. Group I 
      received PG-APS and was treated with the B2-RA, CP-0597 
      (DArg-Arg-Pro-Hyp-Gly-Thi-Ser-DTic-NChg-Arg). Group II received PG-APS and was 
      treated with a combined B1 and B2-RA, B9430 
      (DArg-Arg-Pro-Hyp-Gly-Igl-Ser-Dlgl-Oic-Arg). Group III received PG-APS and 
      albumin control. Group IV received albumin control. METHODS: Joint diameter, 
      liver weight, hematocrit, white blood count and plasma concentrations of 
      prekallikrein, high molecular weight kininogen, HK and IL-beta were measured. 
      Groups were compared by ANOVA. RESULTS: Acute arthritis and hepatomegaly were 
      attenuated in the B2-RA-treated animals (p<0.05). Weight loss was more pronounced 
      in the B1/B2-RA-treated animals. Anemia induced by PG-APS was prevented by B2-RA 
      and B1/B2-RA treatment (p<0.001). A marked decrease in plasma HK to 64% of normal 
      was found in the disease-untreated animals, which was completely normalized by 
      B2-RA treatment and partially attenuated by the B1/B2-RA (78%). The decrease in 
      plasma prekallikrein levels was prevented by combined B1/B2-RA treatment 
      (p<0.05). Finally, elevated plasma IL-1beta levels were lowered by B1/B2-RA 
      treatment and were below detection limits with the B2-RA treatment. CONCLUSIONS: 
      These results indicate that the systemic inflammation is due in part to BK 
      generation which can be blocked by B2-RA, while inhibiting the B1 receptor 
      prevents an anti-inflammatory response.
FAU - Uknis, A B
AU  - Uknis AB
AD  - Sol Sherry Thrombosis Research Center, Department of Medicine, Temple University 
      School of Medicine, Philadelphia, PA 19140, USA.
FAU - DeLa Cadena, R A
AU  - DeLa Cadena RA
FAU - Janardham, R
AU  - Janardham R
FAU - Sartor, R B
AU  - Sartor RB
FAU - Whalley, E T
AU  - Whalley ET
FAU - Colman, R W
AU  - Colman RW
LA  - eng
GR  - K08 AR01957/AR/NIAMS NIH HHS/United States
GR  - R01 DK43735/DK/NIDDK NIH HHS/United States
GR  - R41 AR45848/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (B 9430)
RN  - 0 (Bradykinin Receptor Antagonists)
RN  - 0 (CP 0597)
RN  - 0 (Interleukin-1)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptidoglycan)
RN  - 0 (Receptor, Bradykinin B2)
RN  - EC 3.4.21.- (Kallikreins)
RN  - S8TIM42R2W (Bradykinin)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Arthritis/chemically induced/*drug therapy
MH  - Bradykinin/analogs & derivatives/physiology/therapeutic use
MH  - *Bradykinin Receptor Antagonists
MH  - Female
MH  - Inflammation/*prevention & control
MH  - Interleukin-1/blood
MH  - Kallikreins/blood
MH  - Neutrophils/physiology
MH  - Oligopeptides/*therapeutic use
MH  - Peptidoglycan/*toxicity
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Receptor, Bradykinin B2
EDAT- 2001/05/08 10:00
MHDA- 2001/09/14 10:01
CRDT- 2001/05/08 10:00
PHST- 2001/05/08 10:00 [pubmed]
PHST- 2001/09/14 10:01 [medline]
PHST- 2001/05/08 10:00 [entrez]
AID - 10.1007/s000110050739 [pii]
AID - 10.1007/s000110050739 [doi]
PST - ppublish
SO  - Inflamm Res. 2001 Mar;50(3):149-55. doi: 10.1007/s000110050739.