Endothelin-1 and angiotensin-II modulate urotensin-II vasoconstriction in rat aorta exposed to mercury.

OBJECTIVES: The aim of this study was to evaluate the possible roles of endothelin-1 and angiotensin-II in urotensin-II vasoconstriction and in endothelial dysfunction induced by mercury. BACKGROUND: Urotensin-II, the most potent vasoactive peptide, is entwined with the cardiovascular diseases and has been labelled as a new pathophysiological biomarker. METHODS: Rat aortic rings were pre-incubated with sb-710411, bq-123, and captopril. Doses of human urotensin-II with increased concentrations were applied in all groups in the presence or absence of mercury chloride. In another set of the experiment, aortic rings were treated with a single dose of mercury chloride in the presence of each of the above blockers. RESULTS: Angiotensin-II and endothelin-1 mediated the vascular responses to the peptide urotensin-II under conditions of both intact endothelium and endothelial impairments induced by mercury. Urotensin-II, angiotensin-II and endothelin-1 significantly participated in vascular responses to mercury chloride. CONCLUSION: The novel finding was that urotensin-II is potentiated under the condition of endothelial dysfunction. Endothelin-1 and angiotensin-II pathways could be heavily exploited in modulating endothelial dysfunction impacts and peptide vascular actions (Tab. 1, Fig. 4, Ref. 30).

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

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.