Des-Arg9-bradykinin causes kinin B1 receptor mediated endothelium-independent contractions in endotoxin-treated porcine coronary arteries.
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.
['More|Amar S|AS|', 'Kim|Hye Min|HM|', 'Khang|Gilson|G|', 'Hildebrandt|Tobias|T|', 'Bernlöhr|Christian|C|', 'Doods|Henri|H|', 'Vanhoutte|Paul M|PM|', 'Wu|Dongmei|D|']
D000818:Animals D001920:Bradykinin D065169:Bradykinin B1 Receptor Antagonists D003331:Coronary Vessels D051545:Cyclooxygenase 1 D051546:Cyclooxygenase 2 D004149:Dioxoles D004730:Endothelium, Vascular D066298:In Vitro Techniques D008070:Lipopolysaccharides D012333:RNA, Messenger D043783:Receptor, Bradykinin B1 D043782:Receptor, Bradykinin B2 D013449:Sulfonamides D013552:Swine D013930:Thromboxane-A Synthase D014661:Vasoconstriction
Kinin B1 receptor Cyclooxygenase-2 Vascular contraction Vascular inflammation