Functional antagonism between calcium-antagonists and noradrenaline on isolated guinea-pig atria.

In the isolated electrically driven guinea-pig atrium the influence of D 600 and nifedipine on the action of noradrenaline was investigated. 1. The calcium-antagonists caused a dose-dependent negative inotropic effect. 10(-7) M of D 600 or nifedipine inhibited the contractile amplitude by 75 and 55%, respectively. 2. In spite of the pronounced negative inotropic effect evoked by the two calcium-antagonists, the maximal response to noradrenaline was not changed. The sensitivity of the myocardium to noradrenaline was only slightly diminished i.e. by a factor of 4.6 and 3 as calculated from the pD2-values. 3. The functional antagonism between noradrenaline and calcium-antagonists, therefore, offers the possibility to overcome cardiac side-effects of calcium-antagonists.