Additional experimental evidence was obtained for an inhibitory function of prejunctional alpha 2-adrenoceptors and/or dopamine receptors located on noradrenergic neurons innervating the heart and resistance vessels of the pithed normotensive rat. Mixed alpha 2-adrenoceptor/dopamine receptor agonists, differing in selectivity towards either receptor type, i.e. N,N-di-n-propyldopamine (DPDA), 2-N, N-di-n-propylamino-6, 7-dihydroxy-1,2,3,4-tetrahydro-naphthalene (DP-6,7-ADTN), B-HT 920 and B-HT 933 (azepexole) were used. In pithed normotensive rats, DPDA (30 and 100 micrograms/kg/min) dose-dependently inhibited the electrical stimulation-induced increase in diastolic pressure, but did not significantly affect the stimulation-evoked increase in heart rate. The inhibition exerted by DPDA was blocked by haloperidol and sulpiride (0.3 mg/kg of each), but not by yohimbine (1 mg/kg), indicating the involvement of dopamine receptors. In this respect, sulpiride and haloperidol were found approximately equipotent. DP-6,7-ADTN (10 and 30 micrograms/kg/min) impaired both tachycardic and vasoconstrictor responses in a dose-dependent manner. Sulpiride (0.3 mg/kg) only partially restored the DP-6,7-ADTN-depressed stimulation-evoked increase in diastolic pressure, whereas yohimbine (1 mg/kg) alone was without effect. The combination of both antagonists completely prevented the inhibition caused by DP-6,7-ADTN. On the other hand, yohimbine (1 mg/kg), but not sulpiride (0.3 mg/kg), selectively antagonized the DP-6,7-ADTN-induced inhibition of stimulation-evoked tachycardia. B-HT 920 (1, 3 and 10 micrograms/kg/min) very effectively reduced the increase in diastolic pressure and heart rate caused by electrical stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
