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.

Bradykinin increases BP in endotoxemic rat: functional and biochemical evidence of angiotensin II AT1/bradykinin B2 receptor heterodimerization

“…and COX-2 activities in endothelial cells (Basei et al, 2012). Moreover, endothelium-denuded porcine coronary arteries display contractile responses mediated by B 1 and B 2 receptors after in vitro incubation with LPS More, Kim, Zhao, et al, 2014). Indeed, both pharmacological and molecular approaches did…”

“…For instance, the contractile effects mediated by B 1 receptors in the rat portal vein were associated with increased thromboxane A 2 levels derived from phospholipase A2 and COX‐2 activities in endothelial cells (Basei et al, ). Moreover, endothelium‐denuded porcine coronary arteries display contractile responses mediated by B 1 and B 2 receptors after in vitro incubation with LPS (More, Kim, Khang, et al, ; More, Kim, Zhao, et al, ). Indeed, both pharmacological and molecular approaches did show that LPS is a trigger for up‐regulation of B 1 receptors in the cardiovascular system of rabbits, pigs, mice, and rats (McLean et al, ; Regoli et al, ; Schremmer‐Danninger et al, ).…”

“…Activation of B 2 receptors is one of the most studied effects of bradykinin in the vascular system. Although multiple intracellular pathways may be involved, accumulation of NO‐ and COX‐derived compounds is often found to be the primary mediator of the vascular activity of bradykinin (Burch & Axelrod, ; Campos & Calixto, ; Fasciolo et al, ; Garrett & Brown, ; Miyamoto et al, ; More, Kim, Zhao, et al, ; Palmer et al, ; Regoli et al, ; Sai et al, ; Starr & West, ). Using indomethacin, we were able to show that products of COX did not play any detectable role in bradykinin‐increased BP following exposure to LPS.…”

“…Contractile responses were also found when porcine basilar arteries were stimulated by high concentrations of bradykinin (Miyamoto, Ishiguro, & Nishio, ). Notably, endothelium‐denuded porcine coronary arteries developed contractile response to bradykinin after exposure to endotoxin, which appears to be mediated by both B 1 and B 2 receptors (More, Kim, Khang, et al, ; More, Kim, Zhao, et al, ). Moreover, experimental hypertension resulted in a leftward shift and enhancement of the endothelium‐dependent vasoconstriction induced by bradykinin in the porcine basilar artery (Islam et al, ).…”

Prostaglandin FP receptor antagonists: discovery, pharmacological characterization and therapeutic utility

“…As mentioned above, a variety of PGs influence venous and arterial blood vessel contractility and/or relaxation in the ocular system. In endotoxin‐treated porcine coronary arteries, the bradykinin (BK) B 1 receptor agonist, des‐Arg 9 ‐BK, caused endothelium‐independent contractions of the tissue that were inhibited by COX‐2 inhibitors and a TP receptor antagonist but neither by a COX‐1 inhibitor (aspirin) nor by DP/EP (AH‐6809)‐, FP (AL‐8810)‐ and IP (RO1138452) receptor antagonists (More et al, ,b). However, since AL‐8810 potently and competitively antagonized the contractile effects of free acids of latanoprost, bimatoprost and PGF 2α in isolated rings of human umbilical vein, the involvement of FP receptors in causing these responses was confirmed (Errasti et al, ).…”