Abstract
Our previous in vitro study demonstrated that bradykinin (BK) induced relaxation and contraction of porcine basilar artery (PBA) mediated via activation of endothelial B2 receptors. The main relaxing and contracting factors appeared to be nitric oxide (NO) and prostaglandin (PG) H2, respectively, but not thromboxane A2. After obtaining these findings, we succeeded in cultivating endothelial cells isolated from the PBA. Although PGH2 has different functionally active isoforms, including PGD2, PGE2, and PGF2α, we have not yet clarified which of them is responsible for BK-induced contraction. Therefore, we attempted to quantify NO and PG production from cultured porcine basilar arterial endothelial cells (PBAECs) and to identify which of the PGs was involved in this contraction. The cultured PBAECs produced NO spontaneously, and BK enhanced this production in a concentration-dependent manner. The NO synthase inhibitor Nω-nitro-l-arginine (L-NNA) and the B2 receptor antagonist HOE-140, but not the B1 receptor antagonist des-Arg9, [Leu8]-BK, completely abolished it. In a functional study, PGD2, PGE2, and PGF2α induced concentration-dependent contractions in isolated porcine basilar arterial rings, the order of maximum contraction being PGF2α > PGE2 > PGD2. The cultured PBAECs produced PGD2, PGE2, and PGF2α spontaneously, and BK significantly enhanced the production of PGF2α, but not that of PGD2 and PGE2. The B2, but not B1, antagonist completely abolished the BK-enhanced production of PGF2α. These results suggest that BK induces production of NO and PGF2α simultaneously from PBAECs via B2 receptor activation.
References
Ainslie PN, Brassard P (2014) Why is the neural control of cerebral autoregulation so controversial? F1000 Prim Rep 6:14. doi:10.12703/P6-14, PMID: 24669295
Antonova M (2013) Prostaglandins and prostaglandin receptor antagonism in migraine. Dan Med J 60:B4635, PMID: 23673269
Bevan R, Dodge J, Nichols P, Poseno T, Vijayakumaran E, Wellman T, Bevan JA (1998) Responsiveness of human infant cerebral arteries to sympathetic nerve stimulation and vasoactive agents. Pediatr Res 44:730–739. doi:10.1203/00006450-199811000-00016, PMID: 9803455
Campos AH, Calixto JB (1994) Mechanisms involved in the contractile responses of kinins in rat portal vein rings: mediation by B1 and B2 receptors. J Pharmacol Exp Ther 268:902–909, PMID: 8114004
Gauthier KM, Cepura CJ, Campbell WB (2013) ACE inhibition enhances bradykinin relaxations through nitric oxide and B1 receptor activation in bovine coronary arteries. Biol Chem 394:1205–1212. doi:10.1515/hsz-2012-0348, PMID: 23729620
Golias C, Charalabopoulos A, Stagikas D, Charalabopoulos K, Batistatou A (2007) The kinin system–bradykinin: biological effects and clinical implications. Multiple role of the kinin system–bradykinin. Hippokratia 11:124–128, PMID: 19582206
Gunnett CA, Lund DD, Howard MA III, Chu Y, Faraci FM, Heistad DD (2002) Gene transfer of inducible nitric oxide synthase impairs relaxation in human and rabbit cerebral arteries. Stroke 33:2292–2296. doi:10.1161/01.STR.0000027427.86177.D4, PMID: 12215601
Hashiba Y, Tosaka M, Saito N, Imai H, Shimizu T, Sasaki T (2007) Vasorelaxing effect of the Rho-kinase inhibitor, Y-27632, in isolated canine basilar arteries. Neurol Res 29:485–489. doi:10.1179/016164107X164076, PMID: 17806208
Hortobágyi L, Kis B, Hrabák A, Horváth B, Huszty G, Schweer H, Benyó B, Sándor P, Busija DW, Benyó Z (2007) Adaptation of the hypothalamic blood flow to chronic nitric oxide deficiency is independent of vasodilator prostanoids. Brain Res 1131:129–137. doi:10.1016/j.brainres.2006.11.009, PMID: 17161389
Jadhav V, Jabre A, Lin SZ, Lee TJ (2004) EP1- and EP3-receptors mediate prostaglandin E2-induced constriction of porcine large cerebral arteries. J Cereb Blood Flow Metab 24:1305–1316. doi:10.1097/01.WCB.0000139446.61789.14, PMID: 15625406
Kawai Y, Ohhashi T (1991) Prostaglandin F2α-induced endothelium-dependent relaxation in isolated monkey cerebral arteries. Am J Physiol 260:H1538–H1543, PMID: 2035674
Kinoshita H, Katusic ZS (1997) Nitric oxide and effects of cationic polypeptides in canine cerebral arteries. J Cereb Blood Flow Metab 17:470–480. doi:10.1097/00004647-199704000-00013, PMID: 9143230
Lauredo IT, Forteza RM, Botvinnikova Y, Abraham WM (2004) Leukocytic cell sources of airway tissue kallikrein. Am J Physiol Lung Cell Mol Physiol 286:L734–L740. doi:10.1152/ajplung.00129.2003, PMID: 14660481
Leeb-Lundberg LM, Marceau F, Müller-Esterl W, Pettibone DJ, Zuraw BL (2005) International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol Rev 57:27–77. doi:10.1124/pr.57.1.2, PMID: 15734727
Michiels C, Arnould T, Knott I, Dieu M, Remacle J (1993) Stimulation of prostaglandin synthesis by human endothelial cells exposed to hypoxia. Am J Physiol 264:C866–C874, PMID: 8476019
Miyamoto A, Hashiguchi Y, Obi T, Ishiguro S, Nishio A (2007) Ibuprofen or ozagrel increases NO release and L-nitro arginine induces TXA2 release from cultured porcine basilar arterial endothelial cells. Vasc Pharmacol 46:85–90. doi:10.1016/j.vph.2006.06.018, PMID: 17113355
Miyamoto A, Murata S, Nishio A (2002) Role of ACE and NEP in bradykinin-induced relaxation and contraction response of isolated porcine basilar artery. Naunyn-Schmiedeberg’s Arch Pharmacol 365:365–370. doi:10.1007/s00210-002-0543-0, PMID: 12012022
Miyamoto A, Ishiguro S, Nishio A (1999) Stimulation of bradykinin B2-receptors on endothelial cells induces relaxation and contraction in porcine basilar artery in vitro. Br J Pharmacol 128:241–247. doi:10.1038/sj.bjp.0702783, PMID: 10498858
Miyamoto A, Nakamoto T, Matsuoka Y, Ishiguro S, Nishio A (1998) The role of thromboxane A2 in regulating porcine basilar arterial tone. J Vet Pharmacol Ther 21:223–227. doi:10.1046/j.1365-2885.1998.00135.x, PMID: 9673964
Miyamoto A, Laufs U, Pardo C, Liao JK (1997) Modulation of bradykinin receptor ligand binding affinity and its coupled G-proteins by nitric oxide. J Biol Chem 272:19601–19608, PMID: 9235967
Nithipatikom K, Laabs ND, Isbell MA, Campbell WB (2003) Liquid chromatographic–mass spectrometric determination of cyclooxygenase metabolites of arachidonic acid in cultured cells. J Chromatogr B Anal Technol Biomed Life Sci 785:135–145. doi:10.1016/S1570-0232(02)00906-6, PMID: 12535846
Norel X (2007) Prostanoid receptors in the human vascular wall. Sci World J 7:1359–1374. doi:10.1100/tsw.2007.184, PMID: 17767355
Sipkema P, van der Linden PJ, Fanton J, Latham RD (1996) Responses to mechanical stimuli of isolated basilar and femoral arteries of the Rhesus monkey are different. Heart Vessel 11:18–26, PMID: 9119801
Sun H, Mayhan WG (2001) Superoxide dismutase ameliorates impaired nitric oxide synthase-dependent dilatation of the basilar artery during chronic alcohol consumption. Brain Res 891:116–122. doi:10.1016/S0006-8993(00)03207-8, PMID: 11164814
Tsuji T, Cook DA (1995) Vasoconstrictor mechanism of neuropeptides augmented after endothelial removal in isolated, perfused canine basilar arteries. Neurol Res 17:193–200, PMID: 7543980
Wambi-Kiéssé CO, Katusic ZS (1999) Inhibition of copper/zinc superoxide dismutase impairs NO.-mediated endothelium-dependent relaxations. Am J Physiol 276:H1043–H1048, PMID: 10070090
Wienecke T, Olesen J, Ashina M (2011) Discrepancy between strong cephalic arterial dilatation and mild headache caused by prostaglandin D2 (PGD2). Cephalalgia 31:65–76. doi:10.1177/0333102410373156, PMID: 20974593
Yoshikawa K, Kita Y, Kishimoto K, Shimizu T (2006) Profiling of eicosanoid production in the rat hippocampus during kainic acid-induced seizure: dual phase regulation and differential involvement of COX-1 and COX-2. J Biol Chem 281:14663–14669. doi:10.1074/jbc.M511089200, PMID: 16569634
Conflict of interest
No competing financial interests exist.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Islam, M.Z., Miyagi, K., Matsumoto, T. et al. Bradykinin induces NO and PGF2α production via B2 receptor activation from cultured porcine basilar arterial endothelial cells. Naunyn-Schmiedeberg's Arch Pharmacol 387, 697–702 (2014). https://doi.org/10.1007/s00210-014-0989-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00210-014-0989-x