The Role of Endothelium-Derived Relaxing Factor in The Regulation of SNP Induced Vasorelaxation: Sodium-Potassium-Chloride Cotransporter
Keywords:
NKCC, Bumetanide, SNP, Rat Aorta, EDHF1Abstract
Vascular endothelium plays a key role in the local regulation of vascular tone and vascular architecture. However, it is unclear whether the combination of NKCC cotransporter with endothelial mediated factor and potassium channel in rat aortic ring contributes in regulation of the vascular activity. In the current study, the potential role of endothelium-mediated relaxing factors and potassium channel in SNP induced vasorelaxation in precontracted isolated rat aortic rings in the presence of Bumetanide as NKCC blocker were investigated. The maximum vasorelaxation induced by SNP significantly blocked by the presence BUM. SNP induced relaxation was affected by combination of BUM with Indomethacin, Clotrimazole. TEA and BaCl2 significantly blocked of SNP induced relaxation in aorta preincubated with all blockers used, but BaCl2 showed a more potent effect as compared with others. These results indicate that SNP – induced vasorelaxation was mediated via EETs, Prostaglandin, BKCa and KIR pathways which ultimately enhanced the contribution of chloride transporter in aortic smooth muscle cells hyperpolarization and subsequent relaxation.
References
BULLEY, S. & JAGGAR, J. H. 2014. Cl(−) channels in smooth muscle cells. Pflugers Arch, 466, 861-72.
CHIPPERFIELD, A. R. & HARPER, A. A. 2000. Chloride in smooth muscle. Prog Biophys Mol Biol, 74, 175-221.
GREENBERG, S., MCGOWAN, C., XIE, J. & SUMMER, W. R. 1994. Selective pulmonary and venous smooth muscle relaxation by furosemide: a comparison with morphine. J Pharmacol Exp Ther, 270, 1077-85.
HUGHES, A. D. 1995. Calcium channels in vascular smooth muscle cells. J Vasc Res, 32, 353-70.
KOLTSOVA, S. V., LUNEVA, O. G., LAVOIE, J. L., TREMBLAY, J., MAKSIMOV, G. V., HAMET, P. & ORLOV, S. N. 2009. HCO3-dependent impact of Na+,K+,2Cl- cotransport in vascular smooth muscle excitation-contraction coupling. Cell Physiol Biochem, 23, 407-14.
LOEWEN, M. E. & FORSYTH, G. W. 2005. Structure and function of CLCA proteins. Physiol Rev, 85, 1061-92.
MOTULSKY, H. J. & CHRISTOPOULOS, A. 2003. Fitting Models to Biological Data Using Linear and Nonlinear Regression. A Practical Guide to Curve Fitting. GraphPad Software Inc. , San Diego, CA.
MTABAJI, J. P., MANKU, M. S. & HORROBIN, D. F. 1976. Vascular actions of furosemide and bumetanide on the rat superior mesenteric vascular bed: interactions with prolactin and prostaglandins. Canadian Journal of Physiology and Pharmacology, 54, 357-366.
PALACIOS, J., ESPINOZA, F., MUNITA, C., CIFUENTES, F. & MICHEA, L. 2006. Na+ -K+ -2Cl- cotransporter is implicated in gender differences in the response of the rat aorta to phenylephrine. Br J Pharmacol, 148, 964-72.
PFISTER, S. L., GAUTHIER, K. M. & CAMPBELL, W. B. 2010. Vascular pharmacology of epoxyeicosatrienoic acids. Adv Pharmacol, 60, 27-59.
PICKKERS, P., DORMANS, T. P., RUSSEL, F. G., HUGHES, A. D., THIEN, T., SCHAPER, N. & SMITS, P. 1997. Direct vascular effects of furosemide in humans. Circulation, 96, 1847-52.
SHEKHA, M. S. & AL-HABIB, O. A. M. 2012. Vasorelaxant, antispasmodic and Cardiotonic effect of the Chloroform Fraction of Crataegus aronia on isolated rat muscles. International Journal of Biological and Biomedical Sciences, 1, 6-11.
VALERO, M. S., GARAY, R. P., GROS, P. & ALDA, J. O. 2006. Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and Na-K-Cl cotransporter NKCC1 isoform mediate the vasorelaxant action of genistein in isolated rat aorta. European journal of pharmacology, 544, 126-131.
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