Response of coronary microvascular collaterals to activation of ATP-sensitive K+ channels.
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 microns 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)-3 x 10(-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 microM), 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 microM), an inhibitor of nitric oxide synthase.


CONCLUSIONS
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.
Lamping
K G
KG
Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City 52242, USA. kathryn-lamping@uiowa.edu
Nuno
D W
DW
Brooks
L A
LA
Fujii
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D010847:Picolines / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D010847:Picolines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011714:Pyrans; D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; C061043:aprikalim; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D000109:Acetylcholine; D005905:Glyburide