The roles of potassium channels in contractile response to urotensin-II in mercury chloride induced endothelial dysfunction in rat aorta

Document Type : Full paper (Original article)

Authors

Department of Biology, College of Science, Salahaddin University, Erbil, Iraq

Abstract

Urotensin-II (U-II), the most potent vasoconstrictor that has recently been recognized as a new candidate in cardiovascular dysfunction, might exert vasoconstriction through, at least partially, potassium channels that are predominant in both endothelial and vascular smooth muscle cells (VSMCs). The present study was designed to evaluate the roles of potassium channels in vascular responses to U-II in intact and mercury induced endothelial dysfunction in rat aorta. The study involved pre-incubation of rat aortic rings with potassium channels blockers: charybdotoxin (chtx), tetraethylammonium (TEA), barium chloride (BaCl2), glibenclamide, 4-aminopyridine (4-AP) and clotrimazole. Then vascular responses to increased concentrations of human U-II (hU-II) were applied to each group in the presence and absence of mercury chloride (HgCl2). Urotensin-II efficacy was significantly increased in chtx, TEA and BaCl2 treated groups, while significantly decreased in glibenclamide and clotrimazole treated groups as compared with the control group. In the presence of mercury, hU-II efficacy was significantly changed in all groups except clotrimazole treated group. The novel findings were that potassium channels modulated the vascular contractile responses to hU-II in isolated rat aorta and mercury treatment increased hU-II efficacy and deteriorated potassium signaling.

Keywords


Al Kindi, H; Hafiane, A; You, Z; Albanese, I; Pilote, L; Genest, J and Schwertani, A (2014). Circulating levels of the vasoactive peptide urotensin II in patients with acute coronary syndrome and stable coronary artery disease. Peptides. 55: 151-157.
Almenara, CC; Broseghini-Filho, GB; Vescovi, MV; Angeli, JK; Faria, TDO; Stefanon, I; Vassallo, DV and Padilha, AS (2013). Chronic cadmium treatment promotes oxidative stress and endothelial damage in isolated rat aorta. PloS ONE. 8: e68418.
Angeli, JK; Cruz Pereira, CA; De Oliveira Faria, T; Stefanon, I; Padilha, AS and Vassallo, DV (2013). Cadmium exposure induces vascular injury due to endothelial oxidative stress: the role of local angiotensin II and COX-2. Free Radic. Biol. Med., 65: 838-848.
Behm, D; Mcatee, J; Dodson, J; Neeb, M; Fries, H; Evans, C; Hernandez, R; Hoffman, K; Harrison, S and Lai, J (2008). Palosuran inhibits binding to primate UT receptors in cell membranes but demonstrates differential activity in intact cells and vascular tissues. Br. J. Pharmacol., 155: 374-386.
Bernatova, I (2014). Endothelial dysfunction in experimental models of arterial hypertension: cause or consequence? Biomed. Res. Int., 2014: 1-14.
Bianca, R; Mitidieri, E; Fusco, F; D’Aiuto, E; Grieco, P; Novellino, E; Imbimbo, C; Mirone, V; Cirino, G and Sorrentino, R (2012). Endogenous urotensin II selectively modulates erectile function through eNOS. PLoS ONE. 7: e31019.
Chatenet, D; Létourneau, M; Nguyen, QT; Doan, ND; Dupuis, J and Fournier, A (2013). Discovery of new antagonists aimed at discriminating UII and URP-mediated biological activities: insight into UII and URP receptor activation. Br. J. Pharmacol., 168: 807-821.
Chukwunonso Obi, B; Chinwuba Okoye, T; Okpashi, VE; Nonye Igwe, C and Olisah Alumanah, E (2016). Comparative study of the antioxidant effects of metformin, glibenclamide, and repaglinide in alloxan-induced diabetic rats. J. Diabetes Res., 2016: 1635361.
Crowley, PD and Gallagher, HC (2014). Clotrimazole as a pharmaceutical: past, present and future. J. Appl. Microbiol., 117, 611-617.
Di Villa Bianca, RDE; Mitidieri, E; Fusco, F; D’Aiuto, E; Grieco, P; Novellino, E; Imbimbo, C; Mirone, V; Cirino, G and Sorrentino, R (2012). Endogenous urotensin II selectively modulates erectile function through eNOS. PloS ONE. 7: e31019.
Dixon, R; Hwang, S; Britton, F; Sanders, K and Ward, S (2011). Inhibitory effect of caffeine on pacemaker activity in the oviduct is mediated by cAMP-regulated conductances. Br. J. Pharmacol., 163: 745-754.
Do Rego, JC; Leprince, J; Scalbert, E; Vaudry, H and Costentin, J (2008). Behavioral actions of urotensin-II. Peptides. 29: 838-844.
Elam, C; Lape, M; Deye, J; Zultowsky, J; Stanton, DT and Paula, S (2011). Discovery of novel SERCA inhibitors by virtual screening of a large compound library. Eur. J. Med. Chem., 46: 1512-1523.
Ellinsworth, DC (2015). Arsenic, reactive oxygen, and endothelial dysfunction. J. Pharmacol. Exp. Ther., 353: 458-464.
Ersoy, S; Orhan, I; Turan, N; Şahan, G; Ark, M and Tosun, F (2008). Endothelium-dependent induction of vasorelaxation by Melissa officinalis L. ssp. officinalis in rat isolated thoracic aorta. Phytomedicine. 15: 1087-1092.
Fernandes Azevedo, B; Barros Furieri, L; Peçanha, FM; Wiggers, GA; Frizera Vassallo, P; Ronacher Simões, M; Fiorim, J; Rossi De Batista, P; Fioresi, M and Rossoni, L (2012). Toxic effects of mercury on the cardiovascular and central nervous systems. BioMed. Res. Int., 2012: 949048.
Furieri, LB; Galán, M; Avendaño, MS; García-Redondo, AB; Aguado, A; Martínez, S; Cachofeiro, V; Bartolomé, MV; Alonso, MJ; Vassallo, DV and Salaices, M (2011). Endothelial dysfunction of rat coronary arteries after exposure to low concentrations of mercury is dependent on reactive oxygen species. Br. J. Pharmacol., 162: 1819-1831.
Grgic, I; Kaistha, BP; Hoyer, J and Kohler, R (2009). Endothelial Ca+-activated K+ channels in normal and impaired EDHF-dilator responses--relevance to cardiovascular pathologies and drug discovery. Br. J. Pharmacol., 157: 509-526.
Houston, MC (2011). Role of mercury toxicity in hypertension, cardiovascular disease, and stroke. J. Clin. Hyperten., 13: 621-627.
Huo, L; Zhang, J; Qu, Z; Chen, H; Li, Y and Gao, W (2015). Vasorelaxant effects of Shunaoxin pill are mediated by NO/cGMP pathway, HO/CO pathway and calcium channel blockade in isolated rat thoracic aorta. J. Ethnopharmacol., 173: 352-360.
Jena, S and Chainy, GB (2008). Effect of methylene blue on oxidative stress and antioxidant defence parameters of rat hepatic and renal tissues. Indian J. Physiol. Pharmacol., 52: 293-296.
Ko, EA; Park, WS; Firth, AL; Kim, N; Yuan, JXJ and Han, J (2010). Pathophysiology of voltage-gated K+ channels in vascular smooth muscle cells: modulation by protein kinases. Prog. Biophys. Mol. Biol., 103: 95-101.
Konduru, N; Keller, J; Ma-Hock, L; Groters, S; Landsiedel, R; Donaghey, TC; Brain, JD; Wohlleben, W and Molina, RM (2014). Biokinetics and effects of barium sulfate nanoparticles. Part Fibre Toxicol., 11: 55.
Loirand, G; Rolli-Derkinderen, M and Pacaud, P (2008). Urotensin II and atherosclerosis. Peptides. 29: 778-782.
Macirella, R; Guardia, A; Pellegrino, D; Bernabò, I; Tronci, V; Ebbesson, L; Sesti, S; Tripepi, S and Brunelli, E (2016). Effects of two sublethal concentrations of mercury chloride on the morphology and metallothionein activity in the liver of Zebrafish (Danio rerio). Int. J. Mol. Sci., 17: 361.
Maguire, JJ; Kuc, RE; Kleinz, MJ and Davenport, AP (2008). Immunocytochemical localization of the urotensin-II receptor, UT, to rat and human tissues: relevance to function. Peptides. 29: 735-742.
Nagaraj, R; Almenara, CCP; Broseghini-Filho, GB; Vescovi, MVA; Angeli, JK; Faria, TDO; Stefanon, I; Vassallo, DV and Padilha, AS (2013). Chronic cadmium treatment promotes oxidative stress and endothelial damage in isolated rat aorta. PLoS ONE. 8: e68418.
Omanwar, S; Saidullah, B; Ravi, K and Fahim, M (2014). Vasorelaxant effects of mercury on rat thoracic aorta: the nitric oxide signaling mechanism. Hum. Exp. Toxicol., 33: 904-910.
Onsa-Ard, A; Shimbhu, D; Tocharus, J; Sutheerawattananonda, M; Pantan, R and Tocharus, C (2013). Hypotensive and vasorelaxant effects of sericin-derived oligopeptides in rats. ISRN Pharmacol., 2013, Article ID 7175292 013.
Pantan, R; Onsa-Ard, A; Tocharus, J; Wonganan, O; Suksamrarn, A and Tocharus, C (2014). Endothelium-independent vasorelaxation effects of 16-O-acetyldihydroisosteviol on isolated rat thoracic aorta. Life Sci., 116: 31-36.
Peng, H; Zhang, M; Cai, X; Olofindayo, J; Tan, A and Zhang, Y (2013). Association between human urotensin II and essential hypertension--a 1:1 matched case-control study. PLoS ONE. 8: e81764.
Proulx, CD; Holleran, BJ; Lavigne, P; Escher, E; Guillemette, G and Leduc, R (2008). Biological properties and functional determinants of the urotensin II
receptor. Peptides. 29: 691-699.
Qu, Z; Zhang, J; Gao, W; Chen, H; Guo, H; Wang, T; Li, H and Liu, C (2014). Vasorelaxant effects of Cerebralcare Granule® are mediated by NO/cGMP pathway, potassium channel opening and calcium channel blockade in isolated rat thoracic aorta. J. Ethnopharmacol., 155: 572-579.
Rameshrad, M; Babaei, H; Azarmi, Y and Fouladi, DF (2016). Rat aorta as a pharmacological tool for in vitro and in vivo studies. Life Sci., 145: 190-204.
Russell, FD (2008). Urotensin II in cardiovascular regulation. Vasc. Health Risk Manag., 4: 775-785.
Schirmer, RH; Adler, H; Pickhardt, M and Mandelkow, E (2011). Lest we forget you--methylene blue … . Neurobiol. Aging. 32(12):2325
Su, XL; Zhang, H; Yu, W; Wang, S and Zhu, WJ (2013). Role of KCa3.1 channels in proliferation and migration of vascular smooth muscle cells by diabetic rat serum. Chin. J. Physiol., 56: 155-162.
Tep-Areenan, P and Sawasdee, P (2010). Vasorelaxant effects of 5, 7, 4´-trimethoxyflavone from Kaepmferia parviflora in the rat aorta. IJP-Int. J. Pharmacol., 6: 419-424.
Wrzosek, A (2009). Endothelium as target for large-conductance calcium-activated potassium channel openers. Acta Bioch. Polonica. 56: 393-404.
Wulff, H and Castle, NA (2010). Therapeutic potential of KCa3.1 blockers: recent advances and promising trends. Expert Rev. Clin. Pharmacol., 3: 385-396.
Xiong, ZM; O’donovan, M; Sun, L; Choi, JY; Ren, M and Cao, K (2017). Anti-aging potentials of methylene blue for human skin longevity. Sci. Rep., 7: 2475.