On the assessment of the beta-adrenoceptor blocking activity of propranolol using the rat isolated right ventricle

Two methods for determining pA2 values, the Schild regression and the use of the formula pA2 = pAx + log(x - 1), have been reassessed. The effects of propranolol on the contractile responses of the rat isolated right ventricle to isoprenaline were studied. The inhibitory effect with the lower concentrations of propranolol tested (3 X 10(-9) -10(-7) M) was solely competitive. Thus there was a parallel dextral displacement of the concentration-response curves to isoprenaline with no depression of the maximal responses. Dual antagonism was observed with the higher concentrations of propranolol tested (10(-6) and 3 X 10(-6) M), thereby showing a parallel displacement of the concentration-response curve to the lower concentrations of isoprenaline with a depression of the maximal responses. Without analysis of data for individual concentrations of propranolol on concentration-response curves to isoprenaline, Schild regression did not clearly illustrate that the antagonism was not solely competitive with the higher concentrations of propranolol. We suggest that data for individual concentrations of antagonist should always be analyzed to ascertain whether there has been a parallel shift of the concentration-response curves to agonist prior to determining pA2 values.