Effects of milrinone on contractile responses of guinea pig trachea, lung parenchyma and pulmonary artery.

The effects of milrinone, a bipyridine with known vasodilator activity, on guinea pig tracheal-spirals, lung parenchymal strips and pulmonary artery rings in vitro were compared with the effects of isoproterenol and aminophylline on these tissues. The concentration of milrinone that produced 50% relaxation (IC50) of tracheal spirals constricted by carbachol was 3.6 X 10(-5) M. Isoproterenol (IC50, 9.5 X 10(-8) M) was significantly (P less than .001) more potent and aminophylline (IC50, 1.2 X 10(-4) M) was significantly (P less than .001) less potent than milrinone in this effect. The IC50 for milrinone for lung parenchymal strips contracted by histamine was 3.2 X 10(-5) M, whereas the IC50 for isoproterenol was significantly (P less than .001) less, 1.4 X 10(-7) M; aminophylline produced only limited relaxation of lung parenchymal strips. Milrinone relaxed pulmonary artery rings constricted by norepinephrine with an IC50 of 3.8 X 10(-6) M, whereas neither isoproterenol nor aminophylline produced a 50% relaxation. Pretreatment of tracheal spirals, lung parenchymal strips and pulmonary artery rings with 1.6 X 10(-4) M milrinone inhibited subsequent contraction by carbachol, histamine and norepinephrine, respectively. The relaxant effects of milrinone were not influenced by treatment with atropine, cimetidine, mepyramine, phentolamine or propranolol. However, indomethacin blocked milrinone's relaxant effects on tracheal spirals effectively, but not on pulmonary artery rings or lung parenchymal strips, suggesting distinct modes of action on various tissue types.