Endothelium is required in the vascular spasm induced by tetraethylammonium and endothelin-1 in guinea-pig aorta

1 To investigate the role of endothelium in vascular spasm, we studied the influence of endothelial (ET-1) on the contracting and spasmogenic effect o f the K+-channel blocker, tetraethylammonium (TEA), in aorta rings of reser pine-treated guinea-pigs, perfused with either control (5.5 mM) or elevated (50 mM) glucose concentration. 2 Endothelium-dependent relaxation induced by acetylcholine was lost in rin gs contracted by noradrenaline in the presence of elevated glucose. In cont rol medium, TEA (1-20 mM) induced a sustained tonic contraction, followed b y a phasic spasm, characterized by rhythmic contractions. Elevated glucose, ET-1 (3 nM), or both, reduced the EC50 of TEA-induced tonic contraction, w ithout modifying the maximum contractile effect. 3 In control medium, ET-1 reduced the time before TEA-induced spasm and inc reased the rate of rhythmic contractions. TEA-induced spasm was abolished b y elevated glucose, and restored by ET-1. The spasm induced by TEA and ET-I was amplified by the ETA antagonist, EMD94246, and suppressed by the ETA-E TB antagonist, bosentan. In endothelium-denuded vessels incubated with high glucose and ET-I, TEA evoked only a tonic contraction. 4 In control medium, L-NAME (N-G-nitro-L-arginine methyl ester) abolished T EA-induced rhythmic contractions. L-arginine, but not D-arginine, prevented the effect of L-NAME. In the presence of elevated glucose and ET-1, TEA-in duced spasm was not affected by L-NAME, whereas verapamil, indomethacin, me tyrapone, glybenclamide or apamin abolished the phasic spasm, unmasking the tonic contracture. 5 In conclusion, endothelium plays a regulatory role in the genesis and mai ntenance of TEA-induced rhythmic contractions, through the release endothel ium derived relaxing factor and vasodilating eicosanoids.