title: Inhibition of kinin B1 receptors attenuates pulmonary hypertension and vascular remodeling.
abstract: This study examined whether the kinin B1 receptor is involved in the pathogenesis of pulmonary hypertension, and whether its inhibition could reduce inflammation, pulmonary hypertension, vascular remodeling, and right heart dysfunction. Male Wistar rats underwent left pneumonectomy. Seven days later, the rats were injected subcutaneously with monocrotaline (60 mg/kg). The rats were then randomly assigned to receive treatment with vehicle or with BI113823 (a selective B1 receptor antagonist, 30 mg/kg, twice per day) via oral gavage from the day of monocrotaline injection to day 28. By day 28, BI113823-treated rats had significantly lower mean pulmonary artery pressure, less right ventricular hypertrophy, and pulmonary arterial neointimal formation than that of the vehicle-treated rats. Real-time polymerase chain reaction revealed that there was a significant increase in mRNA expression of B1 receptors in the lungs of monocrotaline-challenged pneumonectomized rats. Treatment with BI113823 significantly reduced macrophage recruitment, as measured via bronchoalveolar lavage. It also markedly reduced CD-68 positive macrophages and proliferating cell nuclear antigen positive cells in the perivascular areas, reduced expression of inducible nitric oxide synthase, matrix metalloproteinase 2 and 9, and B1 receptors compared with measurements in vehicle-treated rats. These findings demonstrate that kinin B1 receptors represent a novel therapeutic target for pulmonary arterial hypertension.
authors: Department of BIN Fusion Technology, Chonbuk National University, Jeonju, South Korea (P.M., D.L., G.K., D.W.); Department of Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany (T.H., C.B., H.D.); and Department of Research, Mount Sinai Medical Center, Miami Beach, FL (D.W.).
authors: Priya
authors: P
authors: Murugesan
authors: Department of BIN Fusion Technology, Chonbuk National University, Jeonju, South Korea (P.M., D.L., G.K., D.W.); Department of Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany (T.H., C.B., H.D.); and Department of Research, Mount Sinai Medical Center, Miami Beach, FL (D.W.).
authors: Tobias
authors: T
authors: Hildebrandt
authors: Department of BIN Fusion Technology, Chonbuk National University, Jeonju, South Korea (P.M., D.L., G.K., D.W.); Department of Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany (T.H., C.B., H.D.); and Department of Research, Mount Sinai Medical Center, Miami Beach, FL (D.W.).
authors: Christian
authors: C
authors: Bernlöhr
authors: Department of BIN Fusion Technology, Chonbuk National University, Jeonju, South Korea (P.M., D.L., G.K., D.W.); Department of Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany (T.H., C.B., H.D.); and Department of Research, Mount Sinai Medical Center, Miami Beach, FL (D.W.).
authors: Dongwon
authors: D
authors: Lee
authors: Department of BIN Fusion Technology, Chonbuk National University, Jeonju, South Korea (P.M., D.L., G.K., D.W.); Department of Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany (T.H., C.B., H.D.); and Department of Research, Mount Sinai Medical Center, Miami Beach, FL (D.W.).
authors: Gilson
authors: G
authors: Khang
authors: Department of BIN Fusion Technology, Chonbuk National University, Jeonju, South Korea (P.M., D.L., G.K., D.W.); Department of Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany (T.H., C.B., H.D.); and Department of Research, Mount Sinai Medical Center, Miami Beach, FL (D.W.).
authors: Henri
authors: H
authors: Doods
authors: Department of BIN Fusion Technology, Chonbuk National University, Jeonju, South Korea (P.M., D.L., G.K., D.W.); Department of Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany (T.H., C.B., H.D.); and Department of Research, Mount Sinai Medical Center, Miami Beach, FL (D.W.). dongmeiwu@bellsouth.net.
authors: Dongmei
authors: D
authors: Wu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D007705:Kinins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D066253:Vascular Remodeling / Q000502:physiology*
chemical_list: D007705:Kinins; D004247:DNA
keywords: hypertension; hypertrophy; inflammation; kinin B1 receptor antagonist; kinins; pulmonary; right heart hypertrophy; right ventricular; vascular remodeling