Determination of the stimulus-response relation for three alpha-adrenergic agonists on rabbit aorta

A standard rabbit thoracic-aorta strip preparation was used to determine the effect of varying preload on KA(the dissociation constant), A50(the concentration that produces half maximal response) and the ratio KA/A50. Additionally, the stimulus-response relationships were obtained for the drug and preload conditions tested. Values of KA and A50 were calculated from dose-response curves obtained for three alpha-adrenergic agonists (phenylephrine, methoxamine and norepinephrine) in the presence and absence of partial irreversible blockade by phenoxybenzamine. For all three drugs, values of KA and A50 were found to be significantly greater at 1/4 gram preload than at 10 gram preload. However, the ratio KA/A50 was found to be independent of preload conditions. The stimulus-response relationships were all found to be non-linear, in contrast to the predictions of classical receptor theory. The significance of the constancy of KA/A50, rather than either KA or A50, and the non-linear relation between drug stimulus and response is discussed in terms of Stephenson's theory of drug action.