Direct actions of gossypol on cardiac muscle.

Gossypol, an orally active male contraceptive, has been reported to produce cardiotoxicity. In the present study, direct actions of gossypol on the heart muscle were examined using atrial muscle preparations isolated from guinea-pig heart. Gossypol (20-30 microM) produced a transient positive chronotropic effect in spontaneously beating right atrial muscle preparations and a transient positive inotropic effect which reached a peak at about 5 min followed by a marked negative inotropic effect in paced left atrial muscle. These effects of gossypol were not affected by blocking concentrations of phentolamine, nadolol or propranolol, cimetidine and atropine. Gossypol inhibited Na+,K+-ATPase isolated from guinea-pig brain, Na+ pump activity in electrically stimulated left atrial muscle preparations of guinea-pig heart and Na+/Ca2+ exchange in Na+-loaded sarcolemmal vesicles obtained from dog heart. Inhibition of Na+/Ca2+ exchange required high concentrations of gossypol and was rapidly reversible whereas Na+,K+-ATPase inhibition was apparently irreversible. These results indicate that micromolar concentrations of gossypol have direct actions on cardiac muscle.