title: 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.
authors.affiliation: Department of Pharmacology, School of Medicine, Eskisehir Osmangazi University, Meselik, Eskisehir 26480, Turkey. kerol@ogu.edu.tr
authors.forename: Kevser
authors.initials: K
authors.lastname: Erol
authors.forename: Basar
authors.initials: B
authors.lastname: Sirmagul
authors.forename: Fatma Sultan
authors.initials: FS
authors.lastname: Kilic
authors.forename: Semra
authors.initials: S
authors.lastname: Yigitaslan
authors.forename: Ali Evrim
authors.initials: AE
authors.lastname: Dogan
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000097:blood; D004177:Dipyrone / Q000494:pharmacology; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology*; D016753:Interleukin-10 / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000097:blood; D009638:Norepinephrine / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D011460:Prostaglandins F / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D001743:Urinary Bladder / Q000502:physiology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D011453:Prostaglandins; D011460:Prostaglandins F; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C024626:bradykinin, des-Arg(9)-; D013928:Thromboxane A2; D004177:Dipyrone; D019001:Nitric Oxide Synthase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3; D015232:Dinoprostone; D001920:Bradykinin; D009638:Norepinephrine