title: Nitric oxide-independent dilation of conductance coronary arteries to acetylcholine in conscious dogs.
abstract: NO and prostacyclin formation cannot entirely account for receptor-operated endothelium-dependent dilation of coronary vessels, since vasodilator responses are not completely suppressed by inhibitors of these agents. Therefore, we considered that another factor, such as an endothelium-derived hyperpolarizing factor described in vitro, may participate in NO- and prostacyclin-independent coronary dilator responses. In conscious instrumented dogs, intracoronary acetylcholine (ACh, 30.0 ng.kg-1.min-1) increased the external epicardial coronary diameter (CD) by 0.18 +/- 0.03 mm (from 3.44 +/- 0.11 mm) when increases in coronary blood flow (CBF) were prevented and increased the CD by 0.20 +/- 0.05 when CBF was allowed to increase. After the administration of intracoronary N omega-nitro-L-arginine methyl ester (L-NAME), CBF responses to ACh were abolished, but CD responses (0.23 +/- 0.05 from 3.22 +/- 0.09 mm) were maintained. Blockade of NO formation was confirmed by reduced CD baselines and blunted flow-dependent CD responses caused by adenosine and transient coronary artery occlusions after L-NAME administration. ACh-induced CD increases resistant to L-NAME and indomethacin were reduced after the administration of intracoronary quinacrine, an inhibitor of phospholipase A2, or proadifen, an inhibitor of cytochrome P-450. Quinacrine or proadifen alone (without L-NAME) did not alter CD responses to ACh, but L-NAME given after proadifen blunted ACh-induced increases in CD. The increases in CD caused by arachidonic acid given after L-NAME + indomethacin were antagonized by proadifen but not altered by quinacrine. Thus, a cytochrome P-450 metabolite of arachidonic acid accounts for L-NAME-resistant and indomethacin-resistant dilation of large epicardial coronary arteries to ACh. Conversely, NO formation is the dominant mechanism of ACh-induced dilation after blockade of the cytochrome P-450 pathway.
authors.affiliation: Department of Physiology, Faculty of Medicine, Université de Montréal, Québec, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Ming
authors.forename: R
authors.initials: R
authors.lastname: Parent
authors.forename: M
authors.initials: M
authors.lastname: Lavallée
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011335:Proadifen / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D009569:Nitric Oxide; D011335:Proadifen; D011796:Quinacrine; D000241:Adenosine; D000109:Acetylcholine; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester