The Role of Inflammation and COX-Derived Prostanoids in the Effects of Bradykinin on Isolated Rat Aorta and Urinary Bladder

Abstract

Bradykinin, a vasoactive peptide, increases during inflammation and induces the formation of prostaglandins through specific receptor activation. Two types of receptors mediate the biological effects of bradykinin, B(1) and B(2) receptors. Although B(2) receptors are present in most tissues, B(1) receptors are expressed after inflammatory stimuli or tissue injury. Bradykinin has a high affinity for B(2) and a low affinity for B(1) receptors, whereas the opposite occurs for des-Arg(9)-bradykinin. Recently, it has been reported that nonsteroidal anti-inflammatory drugs have different inhibitory activities on cyclooxygenase isozymes, COX-1, COX-2, and COX-3. In the present study, we have investigated the contributions of different COX isozyme inhibitions and inflammation on bradykinin-induced effects of isolated rat aorta and urinary bladder smooth muscle contractions. Male Sprague-Dawley rats weighing 200-250 g were used in the study. The vasodilatory responses to bradykinin (1 nM-1 μM) were studied on isolated rat aorta rings contracted with norepinephrine (0.1 μM) following incubation with dipyrone (100, 700, and 2,000 μM). The relaxant responses of dipyrone (100, 700, and 2,000 μM) were also compared on the isolated rat urinary bladder contracted with bradykinin (n = 8). A bacterial lipopolysaccharide was used for the induction of inflammation (n = 8). The levels of PGE(2), PGF(1α), TXB(2), nitric oxide synthase (NOS), IL-10, and TNF-α were all determined in both the plasma and the perfusate of the aorta preparations (n = 5). The vasodilatory activities of bradykinin and des-Arg9-bradykinin were significantly increased upon the inhibition of COX-3 (dipyrone at 100 μM). These effects disappeared in the inflamed group. PGE(2), PGF1α, and TXB(2) were significantly high, but NOS activity was low in the aorta perfusate after the inhibition of COX-3. Dipyrone showed the relaxant activity of the urinary bladder contracted with bradykinin. The vasodilatory activity of des-Arg(9)-bradykinin was in the inflamed group but not in the non-inflamed group. Bradykinin did not contract urinary bladder in inflamed group. The results suggest that COX-induced products may play an important role in the bradykinin-induced rat aortic smooth muscle relaxations.

COX-2 Mediated Induction of Endothelium-independent Contraction to Bradykinin in Endotoxin-treated Porcine Coronary Artery

“…However, this procedure results in the loss endothelium. [32][33][34][35] The present study shows that bradykinin induces contractions mediated by the COX-2 pathway through TP-receptors in endotoxin-treated pig coronary arteries. 40,43 In particular, kinins and cyclooxygenase products are important inflammatory mediators, 3,4,27 and their production increases during inflammation.…”

“…[31][32][33][34][35][36] Bradykinin stimulates cyclooxygenase activity through both kinin B1 and B2 receptors. [31][32][33][34][35][36] Bradykinin stimulates cyclooxygenase activity through both kinin B1 and B2 receptors.…”

The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta

“…In this regard, a COX inhibitor dipyrone, which is suggested to inhibit COX-3, COX-3 + COX-1, and COX-3 + COX-1 + COX-2 at low, moderate, and high concentrations, respectively, was used in combinations with losartan or lisinopril [7,20].…”

“…Then, aortic rings were incubated with dipyrone (10 , and 2 × 10 -3 M) for 15 minutes, and the percentages of the contractions were calculated. The concentrations of dipyrone were chosen twice-fold of IC 50 values which are expected to inhibit COX-3, COX-3 + COX-1, and COX-3 + COX-1 + COX-2, respectively [7,20].…”

Eicosanoids in carcinogenesis

“…Cox-3 inhibition in rats increases PGE2, prostaglandin I2 (PGI2, prostacyclin), and TXA2 levels in rats in both inflammed and non-inflammed tissues suggesting that Cox-1 and Cox-2 are more specific and effective in terms of prostanoid synthesis of PGE2, PGI2, and TXA2 as compared to Cox-3. Furthermore, Cox-3 results in the augmentation of the vasodilatory activity of bradykinin by modifying Cox-1 and Cox-2 [128].…”