Phentolamine and structurally related compounds selectively antagonize the vascular actions of the K channel opener, cromakalim

Abstract

The effects of cromakalim, a novel vasodilator agent believed to open K+ channels, were studied in a range of large and small arteries in vitro. In dog isolated coronary artery, precontracted with U46619 (a thromboxane A2-mimetic), cromakalim caused concentration-dependent relaxation which could be inhibited by phentolamine (10-100 μM). The ability of phentolamine to antagonize cromakalim was selective since it did not affect responses to a number of other vasodilators including isoprenaline, nitroprusside or nicorandil. The effect of phentolamine was not related to its α-adrenoceptor blocking actions since other α-adrenoceptor antagonists (prazosin 10 μM, rauwolscine 10 μM and phenoxybenzam..