Abstract

We have investigated systemically the hypothesis that there exist subtypes of the alpha-1 adrenoceptor in the canine pulmonary artery. The affinity of the alpha-1 adrenoceptor antagonist, prazosin, was assessed by Schild Regression Analysis against the agonists, phenylephrine, norepinephrine and methoxamine, in rings prepared from canine pulmonary artery using the classical technique in which control and treatment concentration-response curves are obtained in every tissue. This technique allows for appropriate corrections to be made in tissue-dependent differences in agonist potency, time-dependent changes in agonist sensitivity and differences in maximum responses that result from nonspecific effects of agonists occurring at higher concentrations, as was found to be the case for methoxamine. Two cumulative concentration-response curves were constructed for each agonist at 2-hr intervals, with the first (control) concentration-response curve being constructed before the addition of prazosin, and the second concentration-response curve obtained 1 hr after exposure to prazosin. Prazosin had similar pA2 values against phenylephrine (9.56), norepinephrine (9.32) and methoxamine (9.35), with slopes of the Schild Regressions not differing significantly from the theoretical value of unity, suggesting that blockade was competitive in all cases. The results provide no evidence for heterogeneity in alpha-1 adrenoceptors in canine pulmonary artery when assessed using the classical method involving two concentration-response curves in a single tissue and allowing for appropriate corrections in tissue-dependent differences and time-dependent changes in agonist response.