The vasorelaxant effects of milrinone and other vasodilators are attenuated by ouabain

The purpose of this study was to investigate the effect of ouabain pretreatment (1 microM) on relaxation induced by milrinone and other reference vasorelaxants in guinea pig aorta. Pretreatment with ouabain for 1 h significantly reduced the threshold concentration and increased the vasoconstrictor potency of phenylephrine. Relaxation by milrinone of aortic rings contracted by phenylephrine or by an equieffective concentration of phenylephrine in the presence of ouabain was significantly attenuated in the presence of ouabain. The effect of all other vasorelaxants tested, which included isosorbide dinitrate, hydralazine, sodium nitroprusside, forskolin, HA 1004, isoproterenol and verapamil, were also significantly reduced in the presence of ouabain. The vasorelaxant effects of milrinone and verapamil were also evaluated in K+-contracted guinea pig aorta. In contrast to results obtained with phenylephrine-contracted vessels, milrinone and verapamil were equipotent as vasorelaxants in K+-contracted vessels in the presence or absence of ouabain. The results show that ouabain not only potentiates the effect of the vasoconstrictor phenylephrine, but also reduces the potency of drugs that cause vasorelaxation in phenylephrine-contracted tissues, regardless of the mechanism of action of the vasorelaxant. These data may have clinical relevance to the concomitant use of vasodilators and digitalis in the treatment of congestive heart failure.