Des-Arg9-bradykinin causes kinin B1 receptor mediated endothelium-independent contractions in endotoxin-treated porcine coronary arteries

Amar S. More, Hye Min Kim, Gilson Khang, Tobias Hildebrandt, Christian Bernlöhr, Henri Doods, Paul M. Vanhoutte, Dongmei Wu

Research output: Contribution to journalArticle

9 Scopus citations

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 PGF [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.

Original languageEnglish (US)
Pages (from-to)18-24
Number of pages7
JournalPharmacological Research
Volume90
DOIs
StatePublished - Dec 2014

Keywords

  • Cyclooxygenase-2
  • Kinin B1 receptor
  • Vascular contraction
  • Vascular inflammation

ASJC Scopus subject areas

  • Pharmacology

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