Relative resistance of functional β2-adrenoceptor-mediated smooth muscle responses to in vitro desensitization

Abstract

The effects of in vitro incubation of rat isolated left atria, pulmonary artery rings, and aortic rings with isoprenaline (10-6M for 6 h) were examined to compare the degree of desensitization of β1- and β2-adrenoceptor-mediated functional responses. The experimental protocols were carefully controlled to exclude influence from persistence of agonist in the tissues after the prolonged exposures, time-dependent changes in tissue sensitivity, and the methods of plotting the data. Concentration-response curves for isoprenaline were constructed before incubation with isoprenaline and, after washout during 1 h, a second curve was obtained. Two protocols were employed: firstly, the preincubation curve was constructed to ensure that a maximum response was obtained (>10-6M) and, secondly, the preincubation curve was constructed to a maximum isoprenaline concentration of 10-6M. Preincubation curves were corrected for time-dependent changes in sensitivity from sham-incubation control experiments. There was significant desensitization of the β1-adrenoceptor-mediated positive inotropic responses of the left atria, using both protocols, seen as rightward shifts (dose ratios: 4.48 ± 1.12 and 8.39 ± 2.3) of the concentration-response curves and depression of the maximum responses (77.0 ± 3.2 and 60.8 ± 5.5%). In contrast, the β2-adrenoceptor-mediated relaxations of the noradrenaline-constricted pulmonary artery and aorta did not display a significant loss of sensitivity. When the relaxation responses were plotted as a percentage of the noradrenaline-induced tone, there was no significant rightward shift of the concentration-response curves in the pulmonary artery (dose ratios: 2.82 ± 1.33 and 2.24 ± 0.62) or aorta (dose ratios: 1.43 ± 0.62 and 1.31 ± 0.27) and thus no desensitization.Key words: rat atria, pulmonary artery, aorta, β-adrenoceptors, desensitization.