Comparison between the cardiac effects induced by muzolimine and furosemide in guinea-pig atria

Muzolimine (10-500 microM) induced a concentration-dependent reduction of both the contractile force and frequency in spontaneously beating atria and in electrically driven left atrium from reserpine-treated guinea pigs. This negative inotropic response was unaffected by the addition of atropine to the perfusion fluid, and it was highly sensitive to changes in external Ca2+ concentration. Both in spontaneously beating and in electrically driven atrium, muzolimine (50-400 microM) antagonized, in an apparently competitive manner, the increase in contractile force induced by cumulative addition of CaCl2 (0.68-9.59 mM) to the bathing fluid. Muzolimine (50-100 microM) reduced the inotropic response to low (5-30 nM), but not high (50-100 nM) concentrations of Bay K 8644, a calcium-channel agonist. The inotropic effects of 8-phenyltheophylline and of ouabain were antagonized by muzolimine (10-100 microM) in a noncompetitive manner, while the response to noradrenaline was not altered. Similar to muzolimine, verapamil at a concentration suitable to block calcium channels inhibited, in a noncompetitive way, the inotropic effect induced by 8-phenyltheophylline and by ouabain without altering the contractile response to noradrenaline. Furosemide (10 and 100 microM) did not influence the contractile force or the frequency of spontaneously beating atria, nor the inotropic effect induced by CaCl2, 8-phenyltheophylline, ouabain, or noradrenaline. These results indicate that the influence of muzolimine on guinea-pig atria originates from an inhibition of Ca2+ influx into cardiac cells and that furosemide does not mimic the effect of muzolimine at this level.