Comparison of the effects of the K⁺‐channel openers cromakalim and minoxidil sulphate on vascular smooth muscle

Abstract

1The actions of the potassium channel openers, cromakalim and minoxidil sulphate, were compared in a range of isolated blood vessel preparations. 2 Cromakalim and minoxidil sulphate inhibited spontaneous mechanical activity of the guinea-pig portal vein and relaxed the noradrenaline precontracted rat aorta with similar potency. In contrast, minoxidil sulphate was less potent than cromakalim in inhibiting spontaneous activity in the rat portal vein and was essentially inactive in the noradrenaline precontracted rat mesenteric artery and rabbit aorta. 3 Minoxidil sulphate did not antagonize the effects of cromakalim in the rabbit aorta indicating it was not acting as a partial 'agonist'. 4 Charybdotoxin, noxiustoxin and rubidium failed to discriminate between cromakalim and minoxidil sulphate indicating that the apparently selective effects of minoxidil sulphate were not mediated by either Ca2 +-activated potassium channels, delayed rectifiers or rubidium impermeable potassium channels. 5 Glibenclamide antagonized the effects of cromakalim in an apparently competitive manner whereas the effects of minoxidil sulphate were antagonized in a non-competitive manner. The involvement of subtypes of ATP-sensitive potassium channels is discussed.

Vascular Pharmacology of ATP-Sensitive K⁺ Channels: Interactions between Glyburide and K⁺ Channel Openers

“…pinacidil and nicorandil [7,21], More recently. Wickenden et al [17] reported that MNXS behaved somewhat differently than cromakalim depend ing on the vascular preparation. A significant difference was the lack of an effect of MNXS compared to croma kalim in rat mesenteric artery and rabbit aorta, although both agents were similar when tested in rat aorta or rat portal vein.…”

Levcromakalim may induce a voltage‐independent K‐current in rat portal veins by modifying the gating properties of the delayed rectifier

“…In whole portal veins, responses to levcromakalim are insensitive to selective inhibitors of BKca (Winquist et al, 1989;Wickenden et al, 1991;Garcia & Kaczorowski, 1992).…”

ATP‐sensitive K+ channels: Pharmacologic properties, regulation, and therapeutic potential

“…Whereas cromakalim uniformly relaxes a variety of vascular smooth muscles, the actions of minoxidil sulfate are more selective [Wickenden et al, 1991;Winquist et al, 1989;Piper and Hollingsworth, 19891 [Garrino et al, 1989;Plant et al, 19891. On these bases, a possible interaction of minoxidil sulfate at one subtype of sulfonylurea-sensitive K + channel has been suggested [Wickenden et al, 19911.…”