Studies on the temperature-dependent sensitivity of mouse atria to adrenergic drugs

The sensitivity of mouse atria (chronotropic response) to beta-adrenergic receptor antagonists was examined at 37 and 26 degrees C under various experimental conditions. When isoproterenol was used as agonist, at 37 degrees C, the pA2 value (from pA2 plots) for propranolol was 8.86 and the slope of the regression line was 0.54. At 26 degrees C, the pA2 value for propranolol was 9.2 and the slope was 0.7. In the presence of tropolone, 10-5 M, the values for pA2 and slope of the regression lines were, respectively, 9.0 and 0.90 at 37 degrees C and 9.17 and 0.98 at 26 degrees C. In other words, decreasing antagonism was prevented by low temperature and tropolone. Isoproterenol was potentiated by tropolone and low temperature, but the effects of low temperature were reduced by tropolone. With sotalol as antagonist, there was greated blockade (dose ratios) of the effects of isoproterenol at 26 than at 37 degrees C. When nylidrin, a non-catecholamine, was used as agonist there was no temperature-dependent sensitivity to sotalol. Furthermore, nylidrin was not potentiated by low temperature. The data show that the observed degree of beta-receptor antagonism can be altered by changing the bath temperature and suggest that this effect is related to COMT activity or an influence of agonist disposition in the tissue.