Influence of the dopamine receptor agonists fenoldopam and quinpirole in the rat superior mesenteric vascular bed

Abstract

1 The effect of local administration of the dopamine2 (DA2)-receptor agonist quinpirole and of the DA,-receptor agonist fenoldopam was studied in the in situ, constant flow autoperfused, superior mesenteric vascular bed of the rat.2 Local infusion of quinpirole (30 pg kg-'min-' for 5min) 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.3 The inhibitory effect of quinpirole was antagonized by the selective DA2-receptor antagonist domperidone (10 pg kg-') but not by the selective DA,-receptor antagonist SCH 23390 (50 pg kg-'). 4 Local infusion of fenoldopam (30 pg kg-' min-' for 5 min) reduced baseline perfusion pressure to 89.9 ± 1.9%, increased the pressor response to electrical stimulation (4Hz, 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 a,-adrenoceptor agonist phenylephrine were also reduced by fenoldopam (to 38.4 ± 6.4%), but responses to locally administered angiotensin II were not modified.5 Pretreatment with SCH 23390 (50 pg kg-') 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.6 Pretreatment with the selective az-adrenoceptor antagonist rauwolscine (100 pg kg-') 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 a,-adrenoceptors, while its potentiating effect on neurogenic vasoconstriction is due to blockade of presynaptic oi2-adrenoceptors.

Fenoldopam—but not dopamine—selectively increases gastric mucosal oxygenation in dogs

“…However, because we did not measure regional blood flow, it remains unclear if this was caused by an increase in total gastric perfusion or by an intramural redistribution of blood flow toward the gastric mucosa (31). The effects of fenoldopam were abolished by DA 1 -receptor blockade, implying that other vasodilatory mechanisms [e.g., ␣ 1 -antagonism as described for fenoldopam (12)(13)(14)] are negligible. Because DA 1 -receptors are more densely allocated in vessels of the gastrointestinal mucosa compared with vessels of the other layers (31), we speculate that this might facilitate the redistribution of blood flow toward the mucosa.…”

“…Stimulation of ␣ 1 -adrenoceptors in the splanchnic region causes mesenteric vasoconstriction (9) counteracting the desired, dopamine receptorinduced mesenteric vasodilation. Whereas dopamine may stimulate ␣ 1 -receptors even at low doses (10,11), fenoldopam acts antagonistically on those receptors (12)(13)(14) and may thus provide another vasodilatory pathway. We therefore hypothesized that fenoldopam is superior to dopamine in increasing gastric mucosal oxygenation.…”

Dopamine under α1-blockade, but not dopamine alone or fenoldopam, increases depressed gastric mucosal oxygenation*

“…Thus, we speculated that combining dopamine with a selective ␣ 1 -receptor antagonist unmasks the beneficial effects of DA 1 -stimulation on gastrointestinal mucosal oxygenation. In contrast, fenoldopam acts antagonistically on ␣ 1 -receptors (22)(23)(24) and may thus provide another vasodilatory pathway. We therefore hypothesized that dopamine under ␣ 1 -blockade and fenoldopam are superior to dopamine alone in increasing gastric mucosal oxygenation.…”

Disproportional Decrease in Office Blood Pressure Compared With 24-Hour Ambulatory Blood Pressure With Antihypertensive Treatment

“…Thus, the greater fall in office BP in patients with severely elevated pretreatment BP is caused to a large extent by the reduction of the white coat effect. Because 24-hour ABP is void of white coat and placebo effect, the changes in ABP are smaller and the pretreatment BP level lower, [13][14][15] thereby explaining at least in part why changes in office BP and ABP are not related to each other in a 1:1 fashion. The statistical phenomenon of regression to mean might be also one contributing factor, but it is impossible to quantify the effect size from our data set.…”