Mechanisms involved in relaxation induced by exogenous nitric oxide in pig coronary arteries.
The aim of the present study was to analyze the mechanisms involved in the vasodilator responses elicited by nitric oxide (NO) in segments of porcine posterior descending coronary artery. Exogenous NO (0.1-30 microM) induced concentration-dependent relaxations in segments precontracted with a concentration of the thromboxane A2 mimetic, U-46619 (30-300 nM) that produced a contraction 70% (submaximal contraction) of that elicited by 75 mM K+ (maximal contraction). The relaxations were almost abolished by 6-anilinoquinoline-5,8-quinone (LY-83583, 10 microM), an inhibitor of guanylate cyclase, and with precontraction with 40 or 60 mM K+. Relaxations were reduced by 5 mM tetraethylammonium (TEA), a blocker of Ca(2+)-activated K+ channels (Kca channels) and unaltered by ouabain (500 microM), 4-aminopyridine (1 mM), glibenclamide (10 microM), apamin (1 microM) and charybdotoxin (0.3 microM), inhibitors of sodium pump, voltage-sensitive, ATP-sensitive, small-conductance Kca and large-conductance KcaK+ channels, respectively. These results suggest that the relaxation caused by exogenous NO is mediated by guanylate cyclase activation, with only a slight participation of a hyperpolarizing mechanism mediated by activation of Kca channels.
Hernanz
R
R
Department of Pharmacology and Therapeutics, Faculty of Medicine, Universidad Autónoma, Madrid, Spain.
Alonso
M J
MJ
Baena
A B
AB
Salaices
M
M
Alvarez
L
L
Castillo-Olivares
J L
JL
Marín
J
J
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C041715:6-anilino-5,8-quinolinedione; D006162:Guanylate Cyclase