Possible role of nitric oxide and arachidonic acid pathways in hypoxia-induced contraction of rabbit coronary artery rings.
In isolated coronary arteries, hypoxia induces an increase in tone by releasing an unidentified endothelium-derived contracting factor (EDCF). Isometric force was measured in an isolated rabbit coronary artery ring at 37 degrees C in control and high K+ (40 mM) pre-contracted conditions. Hypoxia (15 mmHg pO2) induced by equilibrating the perfusate with nitrogen. Hypoxia did not affect the resting tone but induced an endothelium-dependent contraction on pre-contracted rings. Inhibitors of nitric oxide (NO) were tested, L-NAME (10(-4) M) totally and L-NMMA (10(-4) M) partially convert the hypoxic contraction to an hypoxic relaxation. The addition of L-arginine (10(-4) or 10(-3) M) did not restore the response. Methylene blue (10( -5) M) and ODQ (1 H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one, 10(-5) M), both inhibitors of guanylate cyclase, also changed the hypoxic contraction into a hypoxic relaxation. Catalase (1200 U/ml), which decomposes hydrogen peroxide (H2O2), and superoxide dismutase (150 U/ml, SOD), a free radical scavenger, did not change the hypoxic response but quinacrine (50 microM), an inhibitor of phospholipase A2, significantly decreased it. Inhibitors of arachidonic acid metabolism (indomethacin, diethylcarbamazine, miconazole) however did not affect the hypoxic response. We conclude that in K+ pre-contracted rabbit coronary artery rings, hypoxia induces a contraction which is nitric oxide and arachidonic acid dependent.
Barbé
C
C
Lab. de Neurophysiologie, Equipe du Préconditionnement du Myocarde, Université d'Angers, Cedex, France.
De Crescenzo
V
V
Diemont
F
F
Bonnet
P
P
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000502:physiology*; D003331:Coronary Vessels / Q000502:physiology*; D000860:Hypoxia; D007477:Ions; D009119:Muscle Contraction; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011817:Rabbits
D007477:Ions; D016718:Arachidonic Acid; D009569:Nitric Oxide; D011188:Potassium; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester