© 1997 by European Society of Cardiology
Copyright © 1997, European Society of Cardiology
Response of coronary microvascular collaterals to activation of ATP-sensitive K+ channels
Department of Internal Medicine and The Cardiovascular Center, College of Medicine, University of Iowa, E314-4 GH, Iowa City, IA 52242, USA
* Corresponding author. Tel.: +1 (319) 356-2881; fax: +1 (319) 353-6343; e-mail: kathryn-lamping@uiowa.edu
Objective: Studies have suggested that collateral vessels of the coronary and hind-limb circulations are more sensitive to activation of ATP-sensitive K+ channels than are non-collateral vessels. The objective of the present study was to compare responses of microvascular non-collaterals, native collaterals and stimulated collaterals in the heart to three vasodilators which act through different mechanisms: activation of ATP-sensitive K+ channels with aprikalim, release of nitric oxide with acetylcholine, and endothelium-independent activation of soluble guanylate cyclase with nitroglycerin. Methods: Collateral growth was stimulated by placing an Ameroid occluder on the proximal left circumflex artery in dogs. Non-collaterals, native collaterals and stimulated collaterals (100–220 µm in diameter) were isolated, cannulated on micropipettes and pressurized in vitro. Vessel diameters were measured using videomicroscopy. Results: Dilation to aprikalim (10–8–10–5 M), acetylcholine (10–9–10–6 M) and nitroglycerin (10–8–3x10–4 M) were similar in non-collateral, native collateral and stimulated collaterals. Dilation of native collaterals to aprikalim and acetylcholine was attenuated by glibenclamide (10 µM), an inhibitor of ATP-sensitive K+ channels, but not by tetraethylammonium (1 mM), a non-selective inhibitor of K+ channels. Dilation of native collaterals to acetylcholine but not aprikalim was also inhibited by nitro-L-arginine (10 µM), an inhibitor of nitric oxide synthase. Conclusion: These findings suggest that microvascular native and stimulated collaterals respond to activation of ATP-sensitive K+ channels and acetylcholine similar to non-collaterals of similar size. Thus, changes in reactivity of collaterals to activation of ATP-sensitive K+ channels are not related to changes in the ability of the vessels to respond to vasodilators but may primarily be determined by a change in the distribution of collateral vessel size.
KEYWORDS Aprikalim; Tetraethylammonium; Acetylcholine; Nitric oxide; Nitroglycerin; Potassium channel opener; Potassium channel, ATP sensitive; Dog, arteries; Collateral circulation