Exogenous vasopressin dose-dependently modulates gastric microcirculatory oxygenation in dogs via V1A receptor

Richard Truse,Christian Vollmer,Tabea Mettler-Altmann,Olaf Picker,Inge Bauer,Steven Grewe,Anna Herminghaus,Jan Schulz,Andreas P M Weber

doi:10.1186/s13054-019-2643-y

Abstract

BackgroundHypercapnia improves gastric microcirculatory oxygenation (μHbO2) and increases vasopressin plasma levels, whereas V1A receptor blockade abolishes the increase of μHbO2. The aim of this study was to evaluate the effect of exogenous vasopressin (AVP) in increasing doses on microcirculatory perfusion and oxygenation and systemic hemodynamic variables. Furthermore, we evaluated the role of the vasopressin V1A receptor in mediating the effects.MethodsIn repetitive experiments, six anesthetized dogs received a selective vasopressin V1A receptor inhibitor ([Pmp1, Tyr (Me)2]-Arg8-Vasopressin) or sodium chloride (control groups). Thereafter, a continuous infusion of AVP was started with dose escalation every 30 min (0.001 ng/kg/min–1 ng/kg/min). Microcirculatory variables of the oral and gastric mucosa were measured with reflectance spectrometry, laser Doppler flowmetry, and incident dark field imaging. Transpulmonary thermodilution was used to measure systemic hemodynamic variables. AVP plasma concentrations were measured during baseline conditions and 30 min after each dose escalation.ResultsDuring control conditions, gastric μHbO2 did not change during the course of experiments. Infusion of 0.001 ng/kg/min and 0.01 ng/kg/min AVP increased gastric μHbO2 to 87 ± 4% and 87 ± 6%, respectively, compared to baseline values (80 ± 7%), whereas application of 1 ng/kg/min AVP strongly reduced gastric μHbO2 (59 ± 16%). V1A receptor blockade prior to AVP treatment abolished these effects on μHbO2. AVP dose-dependently enhanced systemic vascular resistance (SVR) and decreased cardiac output (CO). After prior V1A receptor blockade, SVR was reduced and CO increased (0.1 ng/kg/min + 1 ng/kg/min AVP).ConclusionsExogenous AVP dose-dependently modulates gastric μHbO2, with an increased μHbO2 with ultra-low dose AVP. The effects of AVP on μHbO2 are abolished by V1A receptor inhibition. These effects are independent of a modulation of systemic hemodynamic variables.

Highlights

Hypercapnia improves gastric microcirculatory oxygenation and increases vasopressin plasma levels, whereas V1A receptor blockade abolishes the increase of Microcirculatory oxygenation (μHbO2)
During control conditions gastric μHbO2 remained stable throughout the experiment
Further dose escalation to 0.1 ng/kg/min did not change μHbO2 compared to baseline values (81 ± 9%), whereas 1 ng/kg/min Arginine vasopressin (AVP) strongly reduced gastric μHbO2 to 59 ± 16%

Summary

Introduction

Hypercapnia improves gastric microcirculatory oxygenation (μHbO2) and increases vasopressin plasma levels, whereas V1A receptor blockade abolishes the increase of μHbO2. We could show that hypercapnia increased gastric μHbO2 in anesthetized dogs [11] and preserved intestinal μHbO2 in septic rats [12] Both effects were abolished during V1A receptor blockade indicating an involvement of the vasopressin system. Hypercapnia has been shown to cause a slight increase in vasopressin plasma concentration [13, 14], whereas administration of 0.03 U/min vasopressin results in a profound rise in vasopressin plasma levels [6] This suggests that the increase of μHbO2 is mediated via V1A receptors due to increase of endogenous vasopressin plasma levels under hypercapnia. No doseresponse studies exist in a large animal model with the focus on a vasopressin dosage considerably below the clinically used dosage of 0.02–0.04 U/min

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