Relaxation of rat resistance arteries by acetylcholine involves a dual mechanism: activation of K+ channels and formation of nitric oxide.
The relaxation of rat mesenteric resistance arteries to acetylcholine was studied in vessels (normalised internal diameter 230-330 microns) mounted in an isometric myograph and contracted with noradrenaline (5 microM). Removal of the endothelium abolished acetylcholine-induced vasorelaxation, whereas pretreatment with NG-nitro-L-arginine (500 microM) only inhibited the response partly. The relaxation was, however, completely inhibited by NG-nitro-L-arginine when the arteries were contracted with 80 mM K+. Acetylcholine-induced vasorelaxation was also attenuated by pretreatment with the K+ channel blocker, iberiotoxin (100 nM), and the combined pretreatment with iberiotoxin+NG-nitro-L-arginine completely blocked vasorelaxation to acetylcholine. Further, vasorelaxation to acetylcholine was attenuated by tetraethylammonium (5 mM), 4-aminopyridine (1 mM), and BaCl2 (100 microM), respectively, whereas glibenclamide (1 microM) and indomethacin (10 microM) were devoid of effect. Vasorelaxation to the nitric oxide donor sodium nitroprusside was not influenced by iberiotoxin. We conclude that in rat mesenteric resistance arteries, there is a significant nitric oxide-independent component of acetylcholine-induced vasorelaxation, which is mediated by activation of several types of K+ channels, in particular large conductance Ca(2+)-dependent K+ channels.
Hansen
P R
PR
Department of Medicine B2142, Rigshospitalet, University of Copenhagen, Denmark.
Olesen
S P
SP
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D014655:Vascular Resistance / Q000187:drug effects*
D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019335:Nitroarginine; D009569:Nitric Oxide; C064719:iberiotoxin; D000109:Acetylcholine; D011188:Potassium; D009638:Norepinephrine