The Effects of Glycerl Trinitrate and Adenosine 5-Triphosphate On Activation of Potassium Channel-Mediated Vasorelaxation in Female Rats Aortic Smooth Muscle
Nitric oxide (NO) is produced from virtually all cell types composing the cardiovascular tissue and regulates vascular function through fine regulation of excitation–contraction coupling. Endogenous metabolites play a major role in coronary autoregulation. Therefore, the aim of the present study is to investigate the contribution of Glyceryl trinitrate (GTN) and Adenosine 5-triphosphate (ATP) mediated relaxation in rat aortic smooth muscle in intact and endothelium denuded endothelium rings precontracted with Phenylephrine (PE). The thoracic aorta was isolated, cut into rings, and mounted in organ-bath chambers and isometric tension was recorded using PowerLab Data Acquisition System (Model ML 870). The results showed that GTN as NO donor produced dose-dependent relaxation in intact aortic rings precontracted with PE (1 µM) that disinhibited in the presence of Glibenclamide (GLIB), while GLIB attenuate the response induced by ATP in intact aortic rings. L-nitroarginine methylester (L-NAME) an antagonist for nitric oxide synthases (NOS), not abolish the response induced by GTN (Emax 55.28% ± 0.18). Caffeine, ATP receptors antagonist, were partially inhibit the relaxation induced by ATP (vasodilation rate decreased by about 20.57 %). In endothelium denuded aortic rings, vasorelaxation induced by ATP were significantly attenuated, while GTN significantly increased relaxation by removing endothelium. These results suggested that (1) ATP-dependent potassium channel did not involve in GTN inducing vasorelaxation while KATP and A2B receptors have a role in ATP mediated vasorelation (2) ATP partially dependent on endothelium in contrast to NO donors that independent to endothelium.
Bailey, J. C., Feelisch, M., Horowitz, J. D., Frenneaux, M. P., & Madhani, M. (2014). Pharmacology and therapeutic role of inorganic nitrite and nitrate in vasodilatation. Pharmacol Ther, 144(3), 303-320.
Carvajal, J. A., Germain, A. M., Huidobro-Toro, J. P., & Weiner, C. P. (2000). Molecular mechanism of cGMP-mediated smooth muscle relaxation. J Cell Physiol, 184(3), 409-420.
Crecelius, A. R., Kirby, B. S., Richards, J. C., Garcia, L. J., Voyles, W. F., Larson, D. G., . . . Dinenno, F. A. (2011). Mechanisms of ATP-mediated vasodilation in humans: modest role for nitric oxide and vasodilating prostaglandins. Am J Physiol Heart Circ Physiol, 301(4),
Deveci, E. (2006). Ultrastructural effects of lead acetate on brain of rats. Toxicol Ind Health, 22(10), 419-422.
Gewaltig, M. T., & Kojda, G. (2002). Vasoprotection by nitric oxide: mechanisms and therapeutic potential. Cardiovasc Res, 55(2), 250-260.
Ho, M. F., Low, L. M., & Rose'Meyer, R. B. (2016). Pharmacology of the Adenosine A3 Receptor in the Vasculature and Essential Hypertension. PLoS One, 11(2), e0150021. doi: 10.1371/journal.pone.0150021 PONE-D-15-47379 [pii]
Kleschyov, A. L., Oelze, M., Daiber, A., Huang, Y., Mollnau, H., Schulz, E., . . . Munzel, T. (2003). Does nitric oxide mediate the vasodilator activity of nitroglycerin? Circ Res, 93(9), e104-112.
MacMillan, D., Kennedy, C., & McCarron, J. G. (2012). ATP inhibits Ins(1,4,5)P3-evoked Ca2+ release in smooth muscle via P2Y1 receptors. J Cell Sci, 125(Pt 21), 5151-5158.
Maneesai, P., Prasarttong, P., Bunbupha, S., Kukongviriyapan, U., Kukongviriyapan, V., Tangsucharit, P., . . . Pakdeechote, P. (2016). Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in L-NAME-Induced Hypertensive Rats via Restoration of eNOS and AT(1)R Expression. Nutrients, 8(3), 122.
Matteo, B., Karl, G., Alexander, K., Michael, R., Doris, K., Walter, G., Bernd, M. (2008). Bioactivation of Nitroglycerin by Purified Mitochondrial and Cytosolic Aldehyde Dehydrogenases. J Biol Chem. , 283((26)), 17873–17880.
Neshat, S., deVries, M., Barajas-Espinosa, A. R., Skeith, L., Chisholm, S. P., & Lomax, A. E. (2009). Loss of purinergic vascular regulation in the colon during colitis is associated with upregulation of CD39. Am J Physiol Gastrointest Liver Physiol, 296(2), G399-405.
Salihi, A. B. Q., & Al-Habib, O. A. M. (2013). The Role of Endothelium and Endothelium-Derived Relaxation Factors in Nitric Oxide-Induced Aortic Relaxation. Journal of University of Zakho, 1(A): 95-100
Shekha, M. S., & Al-Habib, O. A. M. (2013). Relaxant Effects of Rutin on Rat Smooth Muscles. Journal of University of Zakho, 1,(A)(2), 139-144.
Wellman, G. C., & Nelson, M. T. (2003). Signaling between SR and plasmalemma in smooth muscle: sparks and the activation of Ca2+-sensitive ion channels. Cell Calcium, 34(3), 211-229. doi: S0143416003001246 [pii]
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License [CC BY-NC-SA 4.0] that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work, with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online.