Relative resistance of functional beta(2)-adrenoceptor-mediated smooth muscle responses to in vitro desensitization

The effects of in vitro incubation of rat isolated left atria, pulmonary ar tery rings, and aortic rings with isoprenaline (10(-6) M for 6 h) were exam ined to compare the degree of desensitization of beta(1)- and beta(2)-adren oceptor-mediated functional responses. The experimental protocols were care fully controlled to exclude influence from persistence of agonist in the ti ssues after the prolonged exposures, time-dependent changes in tissue sensi tivity, 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(-6) M) and, secondly, the preincubatio n curve was constructed to a maximum isoprenaline concentration of 10(-6) M . Preincubation curves were corrected for time-dependent changes in sensiti vity from sham-incubation control experiments. There was significant desens itization of the beta(1)-adrenoceptor-mediated positive inotropic responses of the left atria, using both protocols, seen as rightward shifts (dose ra tios: 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%). I n contrast, the beta(2)-adrenoceptor-mediated relaxations of the noradrenal ine-constricted pulmonary artery and aorta did not display a significant lo ss of sensitivity. When the relaxation responses were plotted as a percenta ge of the noradrenaline-induced tone, there was no significant rightward sh ift of the concentration-response curves in the pulmonary artery (dose rati os: 2.82 +/- 1.33 and 2.24 +/- 0.62) or aorta (dose ratios: 1.43 +/- 0.62 a nd 1.31 +/- 0.27) and thus no desensitization.