atrial-natriuretic-factor and 8-phenyltheophylline

Atrial natriuretic peptide has been reported to cause vasoconstriction, vasodilation or no change of coronary vascular resistance in isolated perfused hearts or in open chest animal models. Because general anesthesia and acute surgical trauma may perturb baseline coronary hemodynamics and alter responses to experimental interventions, this study examined the effects of human atrial natriuretic peptide (arginine-102-tyrosine-126) and rat atriopeptin II (serine-103-arginine-125) on the coronary circulation of unsedated, awake dogs. Studies were performed in 12 chronically instrumented animals in which a surgically implanted electromagnetic flow probe and intracoronary catheter allowed measurement of left circumflex coronary blood flow during intraarterial administration of the atrial natriuretic peptides. Bolus doses of both human atrial natriuretic peptide and rat atriopeptin II produced dose-dependent coronary vasodilation; the threshold for coronary vasodilation was 0.2 micrograms/kg body weight for both agents. Coronary vasodilation produced by human atrial natriuretic peptide was not antagonized by adenosine receptor blockade or by cyclooxygenase inhibition with indomethacin. Thus, atrial natriuretic peptides produced dose-dependent coronary vasodilation in intact awake dogs that was not dependent on adenosine-mediated or prostaglandin-mediated mechanisms.

Topics: Animals; Atrial Natriuretic Factor; Coronary Circulation; Coronary Vessels; Cyclooxygenase Inhibitors; Dogs; Dose-Response Relationship, Drug; Indomethacin; Injections, Intra-Arterial; Receptors, Purinergic; Theophylline; Vascular Resistance; Vasodilation; Wakefulness

Atriopeptin II has been reported to cause profound coronary vasoconstriction in the isolated perfused guinea pig heart and in the blood perfused canine heart. Consequently, this study was carried out to examine possible mechanisms by which vasomotor effects of human atrial natriuretic peptide (ANP) occur in the canine coronary circulation. Bolus dosages of ANP were administered into the left circumflex coronary artery of in situ dog hearts perfused at constant flow rate. ANP produced dose-related coronary vasodilation with a threshold dosage of 2 ng/kg; a dosage of 2 micrograms/kg caused a 27 +/- 4% decrease in coronary vascular resistance. Coronary vasodilation produced by ANP was not altered by beta-adrenergic blockade with propranolol (1 mg/kg i.v.). In addition, neither adenosine receptor blockade with 8-phenyltheophylline (5 mg/kg i.v.) nor cyclooxygenase inhibition with indomethacin (5 mg/kg i.v.) significantly altered the response to intra-arterial ANP. These data demonstrate that in the in vitro blood perfused canine heart, ANP administered intra-arterially results in coronary vasodilation that does not utilize adenosine-dependent or prostaglandin-dependent mechanisms.

Topics: Animals; Atrial Natriuretic Factor; Coronary Circulation; Dogs; Hemodynamics; Indomethacin; Propranolol; Receptors, Purinergic; Theophylline; Vasodilation