The Roles of Cycloxygenase and Endothelial Derived Hyperpolarizing Factors in Bradykinin-Induced Aortic Relaxation

  • Ali Z. Omar Erbil Polytechnic University
  • Ismail M. Maulood Salahaddin University
Keywords: Bradykinin, Aorta, cycloxigenase, epoxygenase, Kir and KCa 2channels


The present study is designed to investigate the roles of cycloxygenase (COX) and endothelial derived hyperpolarizing factors (EDHF) pathways in bradykinin (BK)-induced aortic relaxation. Here, isolated aortic rings pre-incubated with different ion channel blockers which are; inward rectifier potassium channel blocker (barium chloride; BaCl2), calcium activated Potassium (KCa+2) channel blocker (tetraethylammonium; TEA), cytochrome P450 inhibitor, clotrimazole and cycloxygenase inhibitor and indomethacin. In BaCl2Emax tended to decrease significantly with significant change of PIC50. TEA pre-incubation markedly shifted DRC of BK to the left side and it significantly reduced PIC50. Indomethacin significantly lowered the PIC50 of BK, but it shifted the DRC of BK to the left.  The results suggested that BK relaxes aortic smooth muscle particularly via the enhancement of cycloxygenase and epoxygenase enzymes as well as through opening Kir and KCa+2channels.

Author Biographies

Ali Z. Omar, Erbil Polytechnic University

Shaqlawa Technical Institute, Erbil Polytechnic University, Kurdistan Region, Iraq.

Ismail M. Maulood, Salahaddin University

Dept. of Biology, College of Science, Salahaddin University, Kurdistan Region, Iraq.


Busse, R., Edwards, G., Félétou, M., Fleming, I., Vanhoutte, P. M., & Weston, A. H. (2002). EDHF: bringing the concepts together. Trends Pharmacol Sci, 23(8), 374-380.
Campbell, W. B., & Fleming, I. (2010). Epoxyeicosatrienoic acids and endothelium-dependent responses. Pflügers Archiv-European Journal of Physiology, 459(6), 881-895.
Costa-Neto, C. M., Dillenburg-Pilla, P., Heinrich, T. A., Parreiras-e-Silva, L. T., Pereira, M. G., Reis, R. I., & Souza, P. P. (2008). Participation of kallikrein–kinin system in different pathologies. International immunopharmacology, 8(2), 135-142.
Cuddapah, V. A., Turner, K. L., Seifert, S., & Sontheimer, H. (2013). Bradykinin-induced chemotaxis of human gliomas requires the activation of KCa3. 1 and ClC-3. The Journal of Neuroscience, 33(4), 1427-1440.
Fukada, S. Y., Tirapelli, C. R., de Godoy, M. A., & de Oliveira, A. M. (2005). Mechanisms underlying the endothelium-independent relaxation induced by angiotensin II in rat aorta. J Cardiovasc Pharmacol, 45(2), 136-143.
Honing, M. L., Smits, P., Morrison, P. J., & Rabelink, T. J. (2000). Bradykinin-induced vasodilation of human forearm resistance vessels is primarily mediated by endothelium-dependent hyperpolarization. Hypertension, 35(6), 1314-1318.
Juffermans, L. J., Kamp, O., Dijkmans, P. A., Visser, C. A., & Musters, R. J. (2008). Low-intensity ultrasound-exposed microbubbles provoke local hyperpolarization of the cell membrane via activation of BK Ca channels. Ultrasound in medicine & biology, 34(3), 502-508.
Kakoki, M., & Smithies, O. (2009). The kallikrein-kinin system in health and in diseases of the kidney. Kidney Int, 75(10), 1019-1030. doi: 10.1038/ki.2008.647
Liu, B., Freyer, A. M., & Hall, I. P. (2007). Bradykinin activates calcium-dependent potassium channels in cultured human airway smooth muscle cells. American Journal of Physiology-Lung Cellular and Molecular Physiology, 292(4), L898-L907.
Madeddu, P., Emanueli, C., & El-Dahr, S. (2007). Mechanisms of disease: the tissue kallikrein–kinin system in hypertension and vascular remodeling. Nature Clinical Practice Nephrology, 3(4), 208-221.
Metea, M. R., & Newman, E. A. (2006). Glial cells dilate and constrict blood vessels: a mechanism of neurovascular coupling. The Journal of Neuroscience, 26(11), 2862-2870.
Nakashima, M., Mombouli, J.-V., Taylor, A. A., & Vanhoutte, P. M. (1993). Endothelium-dependent hyperpolarization caused by bradykinin in human coronary arteries. Journal of Clinical Investigation, 92(6), 2867.
Nishijima, Y., Zheng, X., Lund, H., Suzuki, M., Mattson, D. L., & Zhang, D. X. (2014). Characterization of blood pressure and endothelial function in TRPV4‐deficient mice with l‐NAME‐and angiotensin II‐induced hypertension. Physiol Rep, 2(1).
Rahman, A. M., Murrow, J. R., Ozkor, M. A., Kavtaradze, N., Lin, J., De Staercke, C., . . . Quyyumi, A. A. (2014). Endothelium-derived hyperpolarizing factor mediates bradykinin-stimulated tissue plasminogen activator release in humans. J Vasc Res, 51(3), 200-208. doi: 10.1159/000362666
Roman, R. J. (2002). P-450 metabolites of arachidonic acid in the control of cardiovascular function. Physiological reviews, 82(1), 131-185.
Sanchez, J. C., & López-Zapata, D. F. (2011). The role of BKCa channels on hyperpolarization mediated by hyperosmolarity in human articular chondrocytes. General physiology and biophysics, 30(1), 20-27.
Schubert, R., Krien, U., Wulfsen, I., Schiemann, D., Lehmann, G., Ulfig, N., . . . Gago, H. (2004). Nitric oxide donor sodium nitroprusside dilates rat small arteries by activation of inward rectifier potassium channels. Hypertension, 43(4), 891-896.
Sharma, J. N. (2013). The kinin system in hypertensive pathophysiology. Inflammopharmacology, 21(1), 1-9.
Sharma, J. N., & Al-Sherif, G. J. (2011). The Kinin System: Present and Future Pharmacological Targets. American Journal of Biomedical Sciences, 156-169. doi: 10.5099/aj110200156
Tirapelli, C. R., Bonaventura, D., Tirapelli, L. F., & de Oliveira, A. M. (2009). Mechanisms underlying the vascular actions of endothelin 1, angiotensin II and bradykinin in the rat carotid. Pharmacology, 84(2), 111-126. doi: 10.1159/000231974
How to Cite
Omar, A., & Maulood, I. (2017). The Roles of Cycloxygenase and Endothelial Derived Hyperpolarizing Factors in Bradykinin-Induced Aortic Relaxation. Science Journal of University of Zakho, 5(1), 44-47.
Science Journal of University of Zakho