title: Des-Arg9-bradykinin causes kinin B1 receptor mediated endothelium-independent contractions in endotoxin-treated porcine coronary arteries.
abstract: This study examined responses of isolated pig coronary arteries after kinin B1 receptor induction by endotoxin. Des-Arg9-bradykinin (DBK) induced concentration-dependent, endothelium-independent contractions in lipopolysaccharide (LPS)-treated but not untreated arterial rings. The B1-receptor antagonist SSR240612, but not the B2-receptor antagonist HOE140, prevented the endothelium-independent contractions to DBK. The DBK-induced contractions were blocked by indomethacin (nonselective cyclooxygenase [COX] inhibitor), celecoxib (selective COX-2 inhibitor), and terbogrel (thromboxane-prostanoid [TP] receptor antagonist) but not valeryl salicylate (selective COX-1 inhibitor), AH6809 (an E prostanoid [EP] and PGD2 receptor [DP1] receptor antagonist), AL 8810 (a selective PGF2α [FP] receptor antagonist), or RO1138452 (a selective I prostanoid [IP] receptor antagonist). They were attenuated by N-(p-amylcinnamoyl) anthranilic acid (ACA), and by DETCA plus tiron but not by l-NAME. Quantitative RT-PCR revealed excessive up-regulations of mRNA expressions of B1 receptors, COX-2, and thromboxane A synthase 1 (TBXAS1) following LPS incubation, but not of B2 receptors or COX-1. The present data demonstrate that B1 receptors are coupled to COX-2 in causing endothelium-independent contractions in endotoxin-treated pig coronary arteries. Accordingly, kinin B1 receptor induction during inflammation may have a pathological significance in the vasculature, particular in coronary arteries with dysfunctional endothelial cells.
authors.affiliation: WCU program, Department of BIN Fusion Technology, Chonbuk National University, Chonju, Republic of Korea.
authors.forename: Amar S
authors.initials: AS
authors.lastname: More
authors.affiliation: WCU program, Department of BIN Fusion Technology, Chonbuk National University, Chonju, Republic of Korea.
authors.forename: Hye Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: WCU program, Department of BIN Fusion Technology, Chonbuk National University, Chonju, Republic of Korea.
authors.forename: Gilson
authors.initials: G
authors.lastname: Khang
authors.affiliation: CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hildebrandt
authors.affiliation: CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bernlöhr
authors.affiliation: CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Henri
authors.initials: H
authors.lastname: Doods
authors.affiliation: WCU program, Department of BIN Fusion Technology, Chonbuk National University, Chonju, Republic of Korea; State Key Laboratory of Biopharmaceutical Technologies and Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
authors.affiliation: WCU program, Department of BIN Fusion Technology, Chonbuk National University, Chonju, Republic of Korea. Electronic address: dongmei@jbnu.ac.kr.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wu
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D051545:Cyclooxygenase 1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000502:physiology*; D004149:Dioxoles / Q000494:pharmacology; D004730:Endothelium, Vascular; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000502:physiology*; D043782:Receptor, Bradykinin B2 / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology; D013552:Swine; D013930:Thromboxane-A Synthase / Q000235:genetics; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: C487113:2-((3-(1,3-benzodioxol-5-yl)-3-(((6-methoxy-2-naphthyl)sulfonyl)amino)propanoyl)amino)-3-(4-((2,6-dimethylpiperidinyl)methyl)phenyl)-N-isopropyl-N-methylpropanamide; D065169:Bradykinin B1 Receptor Antagonists; D004149:Dioxoles; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D013449:Sulfonamides; C046722:bradykinin, des-Arg(1)-; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D013930:Thromboxane-A Synthase; D001920:Bradykinin
keywords: Cyclooxygenase-2; Kinin B1 receptor; Vascular contraction; Vascular inflammation