Influence of the dopamine receptor agonists fenoldopam and quinpirole in the rat superior mesenteric vascular bed.
The effect of local administration of the dopamine 2 (DA2)-receptor agonist quinpirole and of the DA1-receptor agonist fenoldopam was studied in the in situ, constant flow autoperfused, superior mesenteric vascular bed of the rat. Local infusion of quinpirole (30 micrograms kg-1 min-1 for 5 min) had no effect on baseline perfusion pressure; it reduced the pressor responses to electrical stimulation (4 Hz, 1 ms, supramaximal voltage) of the periarterial sympathetic nerves to 45.6 +/- 2.1% of its original value but did not modify similar pressor responses produced by locally administered noradrenaline. The inhibitory effect of quinpirole was antagonized by the selective DA2-receptor antagonist domperidone (10 micrograms kg-1) but not by the selective DA1-receptor antagonist SCH 23390 (50 micrograms kg-1). Local infusion of fenoldopam (30 micrograms kg-1 min-1 for 5 min) reduced baseline perfusion pressure to 89.9 +/- 1.9%, increased the pressor response to electrical stimulation (4 Hz, 1 ms, supramaximal voltage) of the periarterial nerves to 134.7 +/- 14.0%, but reduced the pressor response to locally administered noradrenaline to 37.2 +/- 8.2%. Similar pressor responses induced by the selective alpha 1-adrenoceptor agonist phenylephrine were also reduced by fenoldopam (to 38.4 +/- 6.4%), but responses to locally administered angiotensin II were not modified. Pretreatment with SCH 23390 (50 micrograms kg-1) antagonized the effect of fenoldopam on baseline perfusion pressure, but had no influence on the effect of fenoldopam on responses to electrical stimulation or to noradrenaline. Pretreatment with the selective alpha 2-adrenoceptor antagonist rauwolscine (100 micrograms kg-1) had no effect on the reduction in baseline perfusion pressure induced by fenoldopam nor on its inhibitory effect on the response to noradrenaline, but it antagonized the stimulatory effect of fenoldopam on the response to electrical stimulation. 7 The results show that quinpirole inhibits neurogenic vasoconstriction in the rat superior mesenteric vascular bed through stimulation of presynaptic DA2-receptors while fenoldopam stimulates postsynaptic vasodilatory DA,-receptors. In addition, our results suggest that the inhibitory effect of fenoldopam on the vasoconstrictor response to noradrenaline may be due to an antagonistic action at postsynaptic alpha-adrenoceptors, while its potentiating effect on neurogenic vasoconstriction is due to blockade of presynaptic alpha 2-adrenoceptors.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004294:Domperidone / Q000494:pharmacology; D004558:Electric Stimulation; D004873:Ergolines / Q000494:pharmacology*; D005260:Female; D018818:Fenoldopam; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D013152:Splanchnic Circulation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014150:Antipsychotic Agents; D001552:Benzazepines; D004873:Ergolines; D014665:Vasodilator Agents; D000804:Angiotensin II; D010656:Phenylephrine; D019257:Quinpirole; D004294:Domperidone; D018818:Fenoldopam; D009638:Norepinephrine