Nitrous oxide constricts epicardial coronary arteries in pigs: evidence suggesting inhibitory effects on the endothelium

Nitrous oxide increases peripheral vascular tone in animals and humans and constricts epicardial coronary arteries in dogs. Current studies sought both to determine whether nitrous oxide caused epicardial coronary artery constriction in a second animal species, pigs, and to investigate mechanisms. Left anterior descending coronary artery diameters were measured by using computer-assisted angiography in intact pigs anesthetized with ketamine and fentanyl. In separate experiments, isolated porcine coronary arteries were used to assess nitrous oxide effects on both vascular tone and norepinephrine overflow. Agonist-induced increases in [Ca2+]i were estimated in cultured porcine coronary endothelial cells. Nitrous oxide caused epicardial coronary artery vasoconstriction in vivo by about 20%. Nitrous oxide did not affect endothelium-dependent relaxations and contractions in isolated vessels. Norepinephrine overflow was increased but only in vessels with endothelium. The anesthetic attenuated Ca2+ mobilization in endothelial cells. We conclude that nitrous oxide induces epicardial coronary artery constriction in pigs and suggest that the mechanism may involve the inhibition of endothelium-dependent norepinephrine turnover.