Different mechanisms of the rabbit pulmonary arterial contraction caused by 5- or 6-hydroxydopamine

The contractile responses of rabbit arterial strips to 5-hydroxydopamine (5-OHDA) or 6-hydroxydopamine (6-OHDA) were assessed in vitro. The 3H efflux from the pulmonary artery after preloading with [3H]noradrenaline was markedly enhanced by 100 microM 5-OHDA or 6-OHDA. In non-superfused strips, 6-OHDA produced a biphasic contraction, an initial small transient and a subsequent large sustained contraction, whereas 5-OHDA elicited a large monophasic contraction. The 6-OHDA-evoked second large contraction was followed by a marked tachyphylaxis after repeated application of the drug. This contraction was greatly diminished by prazosin or cocaine and by pretreatment with reserpine, indicating an indirect action via noradrenaline release. In contrast, the initial contraction caused by 6-OHDA as well as the contraction caused by 5-OHDA was not inhibited by these agents, except prazosin, implying a direct action at the postsynaptic alpha 1-adrenoceptors. In addition, the concentration-response curve for noradrenaline was significantly shifted to the right by pre-addition of 5-OHDA whereas the curve for 5-HT was virtually unaffected. The results thus suggest that 5-OHDA acts as a postsynaptic alpha 1-adrenoceptor agonist.