Nitric oxide inhibition unmasks ischemic myocardium-derived vasoconstrictor signals activating endothelin type A receptor of coronary microvessels

NO plays an important role in the compensatory increase in coronary flow conductance against myocardial ischemia, and NO bioavailability is impaired in various diseases. We tested the hypothesis that, when NO production is inhibited, vasoconstrictor signals from the ischemic myocardium are unmasked. We investigated the involvement of endothelin type A (ETA) receptors in the transduction of the constrictor signal. To detect coronary vasoactive signals derived from ischemic myocardium, we used a bioassay system in which an isolated rabbit coronary microvessel (detector vessel, DV) was placed on beating myocardium perfused by the left anterior descending coronary artery (LAD) of an anesthetized open-chest dog (n = 38). The DV was pressurized to 60 cmH2O throughout the experiment and observed with an intravital microscope equipped with a floating objective. After the intrinsic tone of the DV was established, vehicle (n = 7), Nω-nitro-l-arginine (l-NNA, 100 μmol/l; n = 13), l-NNA + BQ-123 (a selective ETA rece...