Relaxation of human isolated pulmonary arteries by amrinone.
Amrinone, a selective phosphodiesterase III inhibitor, has been developed as a nonglycoside, noncatecholamine agent with positive inotropic effect. In this study, we examined the effect of amrinone on human pulmonary arterial strips in vitro to understand its action on human pulmonary circulation. Amrinone (10(-5)-10(-3) g/ml) caused dose-dependent relaxation of human pulmonary arterial strips precontracted with 60 mM KCl. Preincubation with either meclofenamate (3.1 microM), a cyclooxygenase inhibitor, or L-N(G)-nitroarginine (100 microM), a competitive inhibitor of EDRF/NO, failed to inhibit amrinone-induced pulmonary vasodilation. The cyclic AMP (cAMP) levels in the supernatant of the lung vessel homogenates increased after incubation with amrinone (10(-3) g/ml). These findings indicate that amrinone causes vasodilation of human pulmonary artery in vitro, and suggest a possible role for cAMP in the mechanisms of amrinone-induced pulmonary vasodilation. Because it is suggested that amrinone has not only positive inotropic effect but also pulmonary vasodilative effect in human in this study, we speculate that amrinone could be an useful agent for the treatment of an increase in right heart afterload and consequent pulmonary hypertension and right heart failure after lung resection in human.
Ono
S
S
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Ueda
S
S
Sakuma
T
T
Tanita
T
T
Koika
K
K
Fujimura
S
S
D000328:Adult; D000368:Aged; D000676:Amrinone / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D002316:Cardiotonic Agents; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D001120:Arginine; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D000676:Amrinone