Dopamine-1 receptor stimulation attenuates the vasoconstrictive response to gut ischemia

Abstract

The effects of fenoldopam, a dopamine-1 (DA-1) receptor agonist, were studied in two groups of anesthetized dogs before and after induction of splanchnic ischemia by way of hemorrhage. During the first portion of the experiment, both groups received fenoldopam (1.5 microg x kg(-1) x min(-1)) for 45 min followed by a 45-min washout. During the second portion, hemorrhage (10 ml/kg) was induced, followed by no intervention in group I (controls) and restarting of the fenoldopam infusion in group II. Prehemorrhage, fenoldopam increased composite portal blood flow by 33% (P < 0.01). After hemorrhage-induced splanchnic ischemia, fenoldopam restored portal vein blood flow to near baseline, maintained the splanchnic fraction of cardiac output, and attenuated the rise in gut mucosal PCO(2). DA-1 receptor stimulation increased portal blood flow and redistributed blood flow away from the serosal layer in favor of the mucosa during basal conditions and after hemorrhage, suggesting a more concentrated distribution of splanchnic DA-1 receptors within the mucosal layer vasculature. Fenoldopam maintained splanchnic blood flow during hypoperfusion and attenuated the splanchnic vasoconstrictive response to hemorrhage.

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

“…The observed increased gastric mucosal oxygenation during fenoldopam infusion was caused rather by increased microvascular Ḋ O 2 than by decreasing regional oxygen consumption. 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.…”

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

“…To increase splanchnic tissue oxygenation, catecholamines with activity on dopaminergic DA 1 -receptors, mediating mesenteric vasodilation, have been suggested (3). Moreover, since DA 1 -receptors are densely located in the vessels of the gastrointestinal mucosa compared with other layers, dopaminergics might facilitate intramural redistribution of perfusion toward the mucosa (3)(4)(5). In this context, dopamine has been used commonly, but its effectiveness has been questioned increasingly (6 -8).…”

Dopamine-1 receptor stimulation impairs intestinal oxygen utilization during critical hypoperfusion

“…We (15) previously demonstrated that fenoldopam increases portal blood flow in a similar experimental model. The present study corroborates this effect and also demonstrates that this results in increased splanchnic Ḋ O 2 , which is expected from the augmentation in regional flow.…”

“…In a similar experimental model, we (15) showed that fenoldopam induces a redistribution of gut blood flow away from the serosa and favors the mucosa. Assuming that local perfusion is normally closely matched to local oxygen demands, this drug-induced redistribution could result in a less favorable perfusion heterogeneity and explains the increase in Ḋ O 2crit found for the overall splanchnic circulation.…”

“…Data from our laboratory have shown that DA-1 receptor stimulation increases portal blood flow and redistributes blood flow away from the intestinal serosa in favor of the mucosa during basal conditions and after hemorrhage. In addition, by augmenting the fraction of cardiac output directed to the gut, fenoldopam maintains splanchnic blood flow during systemic hypoperfusion and attenuates the splanchnic vasoconstrictive response to hemorrhage (15). However, the data used to assess the effects of fenoldopam on intestinal oxygen utilization are scarce and available results are conflicting (8,31).…”