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

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.

Sub-therapeutic vasopressin but not therapeutic vasopressin improves gastrointestinal microcirculation in septic rats: A randomized, placebo-controlled, blinded trial

“…The gastrointestinal oxygenation did not change during vasopressin-infusion with 27 mU · kg -1 · h -1 . These dose dependent effects of vasopressin are in line with a recent published trial of our study group under physiological conditions: sub-therapeutic vasopressin increased the gastric oxygenation, whereas therapeutic vasopressin did not show this amelioration [ 22 ]. This slight impact of therapeutic vasopressin on gastrointestinal microcirculation is further in line with one of the rare clinical trials.…”

“…However, despite these differences in the macrohemodynamic parameters, the effect of vasopressin on the intestinal microcirculation seems to be comparable between clinical and preclinical studies [ 18 ]. In therapeutically used or higher dosages of vasopressin the vasoconstrictive V1A effect seems to prevail, whereas in sub-therapeutic dosages vasodilatatory effects of vasopressin like activation of V2 receptors and oxytocin receptors appears to become more important [ 15 , 22 , 46 , 47 ].…”

“…Furthermore, also therapeutic vasopressin-infusions (2–4 U · h -1 ) seem to induce gastrointestinal hypoperfusion [ 20 , 21 ]. In contrast, we observed that sub-therapeutic vasopressin ameliorated gastrointestinal microcirculation under physiologic conditions [ 22 ]. Thus, it seems to be important to elucidate, if sub-therapeutic vasopressin can also be beneficial under septic conditions.…”

Local Mucosal CO2 but Not O2 Insufflation Improves Gastric and Oral Microcirculatory Oxygenation in a Canine Model of Mild Hemorrhagic Shock

“…Hypercapnia is known to increase plasmatic vasopressin levels ( 55 , 56 ). Further, hypercapnia as well as low-doses vasopressin are able to improve microvascular oxygenation under physiological conditions ( 45 , 57 ). Those findings can be transferred into animals undergoing sepsis ( 58 , 59 ).…”

“…If this effect depends on local vasopressin release and signal transmission via vasopressin receptors has to be clarified. The V 1A -receptor is reported to mediate a dose-dependent effect on gastric microcirculation under physiological conditions ( 57 ) and stabilizes intestinal oxygenation during hypercapnia in septic ( 60 ) and hemorrhagic ( 61 ) animals. If the protection of gastric and oral oxygenation by local hypercapnia is mediated by a V 1A -receptor dependent increase in flow homogeneity and related to and improved mitochondrial respiration has to be evaluated in further studies.…”