15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and 8-phenyltheophylline

In the fetal lamb, oxygen-induced pulmonary vasodilation is attenuated by the combined use of purinergic receptor P1 and P2y antagonists, which block the effect of adenosine and adenosine triphosphate (ATP), respectively, and by N(omega)-nitro-L-arginine [an inhibitor of endothelium-derived nitric oxide (EDNO) synthesis]. In the newborn lamb, oxygen-induced pulmonary vasodilation is not blocked by N(omega)-nitro-L-arginine. We investigated the role of ATP and adenosine in oxygen-induced pulmonary vasodilation in eight newborn lambs with pulmonary hypertension induced by the thromboxane mimic, U46619. The hemodynamic effects of hyperoxia, ATP, adenosine, sodium nitroprusside (SNP), and acetylcholine (ACh) were compared before and after purinergic receptor blockade with Cibacron blue (CB, a P2y-receptor antagonist) and 8-phenyltheophylline (8PT, a P1-receptor antagonist) individually, together, and on a separate day, after infusion of N(omega)-nitro-L-arginine. During pulmonary hypertension, combined pretreatment with 8PT and CB attenuated the decrease in pulmonary arterial pressure caused by hyperoxia (11.3 vs. 35.2%), ATP (10.6 vs. 32.2%), and adenosine (1.9 vs. 33.7%) without change in the effect of ACh or SNP (p < 0.05). N(omega)-Nitro-L-arginine attenuated the pulmonary vasodilation caused by ATP and ACh but not by hyperoxia, adenosine, or SNP. In the newborn lamb, the pulmonary vasodilating effect of both oxygen and ATP are attenuated by combined P1 and P2y purinergic-receptor antagonists. Postnatally, oxygen-induced pulmonary vasodilation appears to be mediated by ATP through purinergic receptors.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adenosine; Adenosine Triphosphate; Animals; Animals, Newborn; Endothelium, Vascular; Enzyme Inhibitors; Hemodynamics; Hypertension, Pulmonary; Nitric Oxide; Nitroarginine; Oxygen; Prostaglandin Endoperoxides, Synthetic; Pulmonary Artery; Purinergic Antagonists; Sheep; Theophylline; Thromboxane A2; Triazines; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

The coronary circulation has been shown to remain responsive to vasodilator and vasoconstrictor stimuli during myocardial ischaemia. The aim of this study was to investigate whether endogenous adenosine attenuates coronary vasoconstriction caused by the thromboxane A2 analogue, U46619.. Nine chronically instrumented dogs were studied during treadmill exercise in the presence of a coronary stenosis which resulted in distal left circumflex coronary artery hypoperfusion. Myocardial blood flow was assessed with radioactive microspheres during exercise prior to and during intracoronary infusion of U46619 (0.01 microgram.kg-1 x min-1), in the absence and the presence of adenosine receptor blockade with intravenous 8-phenyltheophylline (5 mg.kg-1) and intracoronary adenosine deaminase (50 units.kg-1). Distal coronary pressure was maintained constant during the control stenosis and the three interventions, at 49(SEM 3), 50(3), 50(3), and 50(3) mm Hg.. During control exercise mean myocardial blood flow was 0.91(0.09) ml.min-1 x g-1 in the stenosis region and 2.54(0.28) in the normal region. With no change in distal coronary pressure, U46619 decreased mean myocardial blood flow to 0.70(0.10) ml.min-1 x g-1 (p < 0.05). Adenosine blockade alone decreased myocardial blood flow in the stenosis region to 0.60(0.07) ml.min-1 x g-1 (p < 0.05 v control stenosis), indicating that endogenous adenosine contributed to coronary vasodilatation in the ischaemic region. However, adenosine blockade did not augment the vasoconstriction in response to U46619 [mean myocardial blood flow 0.49(0.05) ml.min-1 x g-1], indicating that endogenous adenosine did not attenuate the vasoconstriction caused by U46619.. Endogenous adenosine contributed to dilatation of resistance vessels in hypoperfused myocardium of exercising dogs in the absence as well as in the presence of U46619. However, endogenous adenosine did not attenuate the magnitude of the vasoconstrictor response to U46619. These findings are best explained by observations that thromboxane A2 and adenosine act on coronary vascular segments of different size.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adenosine; Animals; Coronary Vessels; Dogs; Myocardial Contraction; Myocardial Ischemia; Physical Exertion; Prostaglandin Endoperoxides, Synthetic; Regional Blood Flow; Theophylline; Thromboxane A2; Vasoconstriction; Vasoconstrictor Agents