BACKGROUND: Etomidate produces minimal cardiovascular effects in clinical uses but their effects on the porcine coronary arteries are not well known yet. We studied the direct effects of etomidate on porcine coronary arterial tone and the underlying mechanism of its vascular relaxation. METHODS: Porcine coronary arterial ring segments (3-4 mm) with or without endothelium were suspended in modified Krebs solution (37oC) and preconstricted with K+ 40 mM. Changes in tension were measured following cumulative administrations of etomidate (10(-5), 5 x 10(-5) and 10(-4) M). Relaxation caused by etomidate (10(-4)M) were measured in the presence of either NG-nitro-L-arginine methyl ether (L-NAME 10(-5)M, n = 13), indomethacin (2.8 x 10(-5)M, n = 12), methylene blue (2 x 10(-5)M, n = 12), tetraethylammonium (TEA, KCa2+ blocker, 20 mM, n = 11), glibenclamide (n = 13) 2.5 x 10(-5)M or 4-aminopyridine (4-AP, K+ DR blocker, 10 4 M, n = 12). Effects of etomidate on Ca2+ influx through the voltage operated channel (VOC) of the vascular cells were also evaluated. RESULTS: Arterial reings were relaxed by etomidate in a concentration-dependent manner and these effects were not affected by endothelium. In the etomidate pretreated group, arterial ring in a calcium-free solution showed no contraction with KCl 40 mM, but the contraction after the administration of calcium 2.5 mM less than without etomidate group (47.2 +/- 8.7% vs 97.7 +/- 10.6%). The other group, not pretreated with etomidate, showed the same vascular tone of the control group in a slow upstroke manner with calcium administration. Pretreatment with either L-NAME, indomethacin and methylene blue did not affect etomidate-induced vasorelaxation. The TEA, glibenclamide and 4-AP pretreated groups also did not affect the vascular relaxation. CONCLUSIONS: Etomidate relaxes the porcine coronary artery in a concentration-dependent manner withor without endothelium, via inhibition of Ca2+ influx through the voltage-operated Ca2+ channel.
4-Aminopyridine ; Calcium ; Coronary Vessels* ; Endothelium ; Ether ; Etomidate* ; Glyburide ; Indomethacin ; Methylene Blue ; NG-Nitroarginine Methyl Ester ; Nitroarginine ; Relaxation ; Tea ; Tetraethylammonium ; Vasodilation