The Role of Inflammation and COX-Derived Prostanoids in the Effects of Bradykinin on Isolated Rat Aorta and Urinary Blad
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The Role of Inflammation and COX-Derived Prostanoids in the Effects of Bradykinin on Isolated Rat Aorta and Urinary Bladder Kevser Erol,1,2 Basar Sirmagul,1 Fatma Sultan Kilic,1 Semra Yigitaslan,1 and Ali Evrim Dogan1
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, B1 and B2 receptors. Although B2 receptors are present in most tissues, B1 receptors are expressed after inflammatory stimuli or tissue injury. Bradykinin has a high affinity for B2 and a low affinity for B1 receptors, whereas the opposite occurs for des-Arg9bradykinin. 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 PGE2, PGF1α, TXB2, 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. PGE2, PGF1α, and TXB2 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-Arg9bradykinin 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. KEY WORDS: bradykinin; inflammation; rat; COX; dipyrone; LPS.
effects, BK is known to elicit relaxation or contraction in vascular and nonvascular smooth muscles [1]. Two types of receptors, B1 and B2, mediate the biological effects of BK [2]. Although B2 receptors are expressed constitutively in most tissues, B1 receptors are expressed only after tissue injury and inflammatory stimuli [3, 4]. B2 receptors are known to be normally constitutive and are predominant to mediate most of the physiological activities of BK [5]. While not normally present in nontraumatized tissue, B1 receptors are upregulated in
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