Study of the negative inotropic action of somatostatin

Somatostatin was evaluated as a chronotropic and inotropic agent in isolated, spontaneously beating guinea-pig atria. Somatostatin (3 x 10(-5)-1 x 10(-3) mM) caused a concentration-dependent negative inotropic effect and a small reduction of atrial rate. The negative inotropic effect of somatostatin was evaluated at different concentrations of extracellular calcium, on the positive inotropic response induced by calcium and on the positive chronotropic response induced by adrenaline. Small, nonsignificant changes in atria response to somatostatin were found both with the lowest (1.25 mM) and with the highest (5 mM) calcium concentration in the medium. Somatostatin (1 x 10(-4)-1 x 10(-3) mm) did not substantially modify the positive inotropic action of calcium; this substance (1 x 10(-3 mM) caused a parallel shift to the right of the adrenaline concentration-response curve. These results suggest that the negative inotropic and chronotropic actions of somatostatin do not appear to be due to an action on the voltage-sensitive calcium channels, but rather to an action on the calcium channels excited by the stimulation of beta-receptors, whose function is probably cooperative with that of the voltage-sensitive channels.