Possible Role of Nitric Oxide and Arachidonic Acid Pathways in Hypoxia-Induced Contraction of Rabbit Coronary Artery Rings

Abstract

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°C in control and high K + (40 mM) pre-contracted conditions. Hypoxia (15 mmHg pO 2) 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 decom-poses hydrogen peroxide (H 2 O 2), and superoxide dismutase (150 U/ml, SOD), a free radical scavenger, did not change the hypoxic response but quinacrine (50 µM), an inhibitor of phospholipase A 2, 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.