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

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: Endothelial dysfunction; Mercury; Potassium channels; Urotensin-II.

Fig. 1

The vascular responsiveness to hU-II from rat thoracic aorta. (A) The effects of endothelial denudation and (B) the effects of HgCl₂ 1 µM on the cumulative doses of hU-II. ^** Represents statistical differences at P<0.01, and ^*** represents statistical differences at P<0.001. Number of animals used is indicated in parentheses

Fig. 2

The effects of HgCl₂ on the vasoconstrictor responses to hU-II in proximal thoracic aorta. (A) Effect of TEA 1 mM, and (B) Effect of chtx 1 µM on the vasoconstrictor responses to hU-II in HgCl₂-treated and untreated aortic rings. The inset graphs show differences in area under the concentration-response curve (dAUC).    ^* Represents statistical differences at P<0.05,     ^** represents statistical differences at P<0.01, and     ^*** represents statistical differences at P<0.001 versus the corresponding control group. Number of animals used is indicated in parentheses

Fig. 3

The effects of HgCl₂ on the vasoconstrictor responses to hU-II in proximal thoracic aorta. (A) Effect of clotrimazole 10 µM, and (B) Effect of BaCL₂ 0.2 mM on the vasoconstrictor responses to hU-II in HgCl₂-treated and untreated aortic rings. The inset graph shows differences in area under the concentration-response curve (dAUC). ^* Represents statistical differences at P<0.05, and ^*** represents statistical differences at P<0.001 versus the control group. Number of animals used is indicated in parentheses

Fig. 4

The effects of HgCl₂ on the vasoconstrictor responses to hU-II in proximal thoracic aorta. (A) Effect of Glib 30 µM, and (B) Effects of 4-AP 0.5 mM on the vasoconstrictor responses to hU-II in aortic rings from control and HgCl₂-treated. The inset graph shows differences in area under the concentration-response curve (dAUC). ^* Represents statistical differences at P<0.05, ^** represents statistical differences at P<0.01, and ^*** represents statistical differences at P<0.001 versus control group. Number of animals used is indicated in parentheses

Fig. 5

The effects of HgCl₂ on the vasoconstrictor responses to hU-II in proximal thoracic aorta. (A) Effect of nifedipine 20 µM, and (B) Effect of L-NAME 200 µM on the vasoconstrictor responses to hU-II in aortic rings from control and HgCl₂-treated. The inset graph shows differences in area under the concentration-response curve (dAUC). ^* Represents statistical differences at P<0.05, ^** represents statistical differences at P<0.01, and ^*** represents statistical differences at P<0.001 versus the control group. Number of animals used is indicated in parentheses

Fig. 6

The effects of HgCl₂ on the vasoconstrictor responses to hU-II in proximal thoracic aorta. Effect of MB 0.8 mM on the vasoconstrictor responses to hU-II in aortic rings from un-treated and HgCl₂-treated groups. The inset graph shows differences in area under the concentration-response curve (dAUC). ^* Represents statistical differences at P<0.05, ^** represents statistical differences at P<0.01, and ^*** represents statistical differences at P<0.001 versus the corresponding control group. Number of animals used is indicated in parentheses