COX-2 mediated induction of endothelium-independent contraction to bradykinin in endotoxin-treated porcine coronary artery.

Abstract

This study examined the vascular effects of bradykinin in health and vascular inflammation comparing responses of isolated pig coronary arteries in the absence and presence of endotoxins. Bradykinin induced contractions in lipopolysaccharide-treated, but not untreated, arterial rings without endothelium. The B2-receptor antagonist HOE140, but not the B1-receptor inhibitor SSR240612, blocked these endothelium-independent contractions in response to bradykinin. The bradykinin-induced contractions were blocked by indomethacin, celecoxib, and terbogrel but not valeryl salicylate, AH6809, AL 8810, or RO1138452. They were attenuated by N-(p-amylcinnamoyl) anthranilic acid, and by diethyldithiocarbamate plus tiron but not by L-NAME. Quantitative reverse-transcription polymerase chain reaction revealed significant upregulations of messenger RNA expressions of B1 receptors, COX-2, and thromboxane A synthase 1 (TBXAS1) following lipopolysaccharide incubation but not of B2 receptors or COX-1. The present data demonstrate that bradykinin induces contractions mediated by the COX-2 pathway in endotoxin-treated pig coronary arteries. These results support differential roles of bradykinin in health and disease.

• Authors: Amar S More, Hye Min Kim, Ru Zhao, Gilson Khang, Tobias Hildebrandt, Christian Bernlöhr, Henri Doods, Dongwon Lee, Seung Hee Lee, Paul M Vanhoutte, Dongmei Wu
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 64 Issue 3 Pg. 209-17 (Sep 2014) ISSN: 1533-4023 [Electronic] United States
• PMID: 25192543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endotoxins
• Lipopolysaccharides
• RNA, Messenger
• Receptor, Bradykinin B1
• Cyclooxygenase 2
• Thromboxane-A Synthase
• Bradykinin

Topics

• Animals
• Bradykinin (metabolism, pharmacology)
• Coronary Vessels (drug effects, metabolism, pathology)
• Cyclooxygenase 2 (genetics, metabolism)
• Endothelium, Vascular (drug effects, metabolism)
• Endotoxins (pharmacology)
• Inflammation (pathology)
• Lipopolysaccharides (pharmacology)
• Muscle Contraction (drug effects)
• RNA, Messenger
• Receptor, Bradykinin B1 (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Swine
• Thromboxane-A Synthase (genetics)
• Up-Regulation