The effects of quinpirole and fenoldopam on the potassium-evoked overflow of endogenous dopamine and noradrenaline in dog mesenteric arteries

Summary

(1) Dopamine and noradrenaline overflow from the main trunk of the dog mesenteric artery and its proximal branches, elicited by K⁺ (52 mmol/l), was measured by high pressure liquid chromatography with electrochemical detection. (2) Quinpirole (0.1, 1 and 10 nmol/l) produced a concentration dependent reduction of dopamine and noradrenaline overflow in both segments of the mesenteric artery. The inhibitory effect of quinpirole (10 nmol/l) on amine overflow was antagonized by sulpiride (1 μmol/l) but not by phentolamine (0.2 μmol/l) or the selective dopamine (DA₁), antagonist SK&F 83566 (1 μol/l). (3) Fenoldopam (0.1 and 1 μmol/l) did not alter dopamine and noradrenaline overflow from both segments of the mesenteric artery; only 10 μmol/l fenoldopam was found to increase the overflow of dopamine and noradrenaline in both segments of the mesenteric artery. This effect of fenoldopam on amine overflow was not altered by the addition to the perifusion fluid of SK&F 83566 (1 μol/l). (4) Clonidine (100 nmol/l) significantly reduced amine overflow from both segments of the mesenteric artery and this effect was antagonized by fenoldopam (10 μmol/l) (5) These results suggest that quinpirole inhibits sympathetic neurotransmission through the activation of prejunctional dopamine receptors of the DA₂ subtype. The facilitatory effect of fenoldopam (10 μmol/l) on amine release appears to be mediated through the blockade of prejunctional α₂-adrenoceptors.