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1The positive inotropic responses of guinea-pig left atria and papillary muscles and positive chronotropic responses of right atria to sympathomimetic amines were examined at 380 and 30°C. 2 At the lower temperature, supersensitivity to orciprenaline and isoprenaline was exhibited as shifts of the dose-response curves to the left and significant reductions in EC50 values. 3 This supersensitivity could not be attributed to reduced metabolism since the experiments were performed in the presence of metanephrine (10-5M) and U-0521 (3',4'-dihydroxy-2-methylpropiophenone) (10-4M) as inhibitors of extraneuronal uptake and catechol-Omethyltransferase (COMT) respectively, and the agonists are not susceptible to neuronal uptake. 4 After incubation of the tissues with Ro 03-7894 (1-(5-chloracetylaminobenzfuran-2-yl)-2-isopropylaminoethanol), followed by its prolonged washout (> 2h), the maximum responses to isoprenaline and orciprenaline were depressed, confirming the apparently irreversible Iadrenoceptor antagonism. 5 Dissociation constants (KA) for isoprenaline and orciprenaline were determined from the equiactive concentrations obtained before (A) and after (A') incubation with Ro 03-7894, plotted as 1/A against 1/A' (KA = (slope -1)/intercept). 6 KA values were the same for orciprenaline in the three cardiac preparations and for isoprenaline in the atria. This applied at 380 and 30°C and indicates that the P-adrenoceptors mediating the inotropic and chronotropic responses of the guinea-pig heart do not differ. 7 The KA values of both agonists were, however, consistently and significantly lower at 300 than at 38°C, indicating an increase in affinity. 8 It is concluded that hypothermia-induced supersensitivity of cardiac tissue to sympathomimetic amines is associated with an increase in their affinity for the ,B-adrenoceptors.

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