XXXX antagonizes the acute relaxant action of @entity2449 on adrenergic contraction in the ventral tail artery of the @entity35 .

@entity1041 @entity5128 @entity973 @entity974 @entity2647 @entity460 @entity972 @entity35 @entity2472 @entity855 @entity2449
The ability of @entity2449 (MF) to acutely relax @entity2647 (PE)-induced contraction in the isolated @entity35 tail artery is reported to be accompanied by repolarization of the arterial smooth muscle cell (SMC) membranes. These membranes contain @entity972 (K) channels which if opened could mediate such repolarization and resultant relaxation. We have shown that the acute relaxation of @entity35 tail arterial tissue rings by graded levels of MF > or = 0.24 mmol/L is markedly antagonized by a high concentration of @entity5128 ( @entity1041 ; 10 mmol/L) which nonselectively inhibits nearly all K channels. Thus, we tested effects of more selective inhibitors of K channels in the same tissue. We also tested MF for relaxation of @entity2472 induced by high levels of extracellular K. To avoid confounding variables, we also conducted these tests in arterial rings in which endothelium and sympathetic nerve endings had been removed. In the absence of K channel inhibition, half-maximal PE-induced @entity2472 were rapidly relaxed by all levels of MF with an EC50 of 1.7+/-0.2 mmol/L (n=8 rings). 1 mmol/L @entity973 ( @entity974 ) which only inhibits voltage-operated and @entity855 -sensitive K channels markedly antagonized this relaxation, shifting the EC50 for MF to 7.5+/-0.7 mmol/L (n=8; p < 0.05). TEA at 1 mmol/L (which only inhibits @entity460 -activated K channels), barium at 20 micromol/L (which only inhibits inward rectifier K channels) and glyburide at 5 micromol/L (which only inhibits @entity855 -sensitive K channels) did not alter this relaxation. Finally, MF failed to relax @entity2472 produced by elevations of extracellular K to levels high enough to abolish the K gradient across arterial SMC membranes. Thus, acute relaxation of @entity35 tail arterial smooth muscle by MF may be dependent on the transmembrane K gradient and mediated at least in part by specific activation of K efflux through 4AP-sensitive voltage-dependent K channels in arterial SMC membranes.
