Effect of dopexamine hydrochloride on sympathetic neuroeffector transmission in rabbit isolated pulmonary artery

The effects of dopexamine hydrochloride on sympathetic neuroeffector transmission were studied in rabbit isolated pulmonary artery. Short-term exposure of dopexamine (10(-8) x 10(-7) M) and cocaine (10(-6)-3 x 10(-5) M), but not desipramine (3 x 10(-9)-3 x 10(-7) M), to the artery enhanced the contractions evoked by electrical-field stimulation. Corticosterone (4 x 10(-5) M), corticosterone (4 x 10(-5) M) plus cocaine (3 x 10(-8) M), but not cocaine (3 x 10(-5) M), attenuated the enhancement seen with dopexamine. High concentrations of dopexamine (10(-5)-3 x 10(-5) M), cocaine (10(-4) M), and desipramine (10(-6)-10(-5) M) decreased the stimulation-evoked contractions. Dopexamine (10(-7)-3 x 10(-5) M), but neither cocaine nor desipramine, caused an increase in resting tension that waned with time. Corticosterone (4 x 10(-5) M), but not cocaine (3 x 10(-5) M), attenuated the increase in resting tension. Propranolol (10(-6) M) did not alter the enhancing and inhibitory effects of dopexamine. A single concentration (10(-7) and 10(-6) M) of either dopexamine or desipramine caused a time-dependent biphasic response as regards the repetitive stimulation-evoked contractions of pulmonary artery: initial enhancement followed by inhibition. The inhibitory effect of dopexamine (10(-6) M) and desipramine (3 x 10(-6) M) seen after prolonged exposure was almost irreversible and partially reversible, respectively, by washing the preparations with drug-free salt solution. Cocaine caused a monophasic steady-state response: either enhancement (10(-5) M) or inhibition (2 x 10(-4) M). In both cases, the onset was rapid. The reduction caused by cocaine (2 x 10(-4) M) and by prazosin (10(-9) M) was fully reversed. Dopexamine (10(-5) M) antagonized competitively the contractions evoked by noradrenaline (3 x 10(-9)-10(-4) M). It is concluded that (1) the dopexamine-induced enhancement of neurogenic contractions is not due to either inhibition of neuronal and extraneuronal uptake of noradrenaline or an agonist action on prejunctional beta 2-adrenoceptors; (2) that the dopexamine-induced inhibition of stimulation-evoked contraction is due to an inhibition of postjunctional alpha 1-adrenoceptors; and (3) that the dopexamine-induced increase in resting tension is due to its metabolite methyldopexamine.