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.
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.
Authors: Jenny Björkqvist; Steven de Maat; Urs Lewandrowski; Antonio Di Gennaro; Chris Oschatz; Kai Schönig; Markus M Nöthen; Christian Drouet; Hal Braley; Marc W Nolte; Albert Sickmann; Con Panousis; Coen Maas; Thomas Renné Journal: J Clin Invest Date: 2015-07-20 Impact factor: 14.808
Authors: Ricardo G Espinola; Audrey Uknis; Irma M Sainz; Irma Isordia-Salas; Robin Pixley; Raul DeLa Cadena; Walter Long; Alexis Agelan; John Gaughan; Albert Adam; Robert W Colman Journal: Am J Pathol Date: 2004-09 Impact factor: 4.307
Authors: James C Keith; Irma M Sainz; Irma Isordia-Salas; Robin A Pixley; Yelena Leathurby; Leo M Albert; Robert W Colman Journal: Arthritis Res Ther Date: 2005-04-04 Impact factor: 5.156
Authors: Pei-Suen Tsou; Chenyang Lu; Mikel Gurrea-Rubio; Sei Muraoka; Phillip L Campbell; Qi Wu; Ellen N Model; Matthew E Lind; Sirapa Vichaikul; Megan N Mattichak; William D Brodie; Jonatan L Hervoso; Sarah Ory; Camila I Amarista; Rida Pervez; Lucas Junginger; Mustafa Ali; Gal Hodish; Morgan M O'Mara; Jeffrey H Ruth; Aaron M Robida; Andrew J Alt; Chengxin Zhang; Andrew G Urquhart; Jeffrey N Lawton; Kevin C Chung; Tristan Maerz; Thomas L Saunders; Vincent E Groppi; David A Fox; M Asif Amin Journal: J Clin Invest Date: 2022-06-01 Impact factor: 19.456