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

BACKGROUND: Hypercapnia improves gastric microcirculatory oxygenation (μHbO(2)) and increases vasopressin plasma levels, whereas V1A receptor blockade abolishes the increase of μHbO(2). 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. METHODS: In repetitive experiments, six anesthetized dogs received a selective vasopressin V1A receptor inhibitor ([Pmp(1), Tyr (Me)(2)]-Arg(8)-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. RESULTS: During control conditions, gastric μHbO(2) did not change during the course of experiments. Infusion of 0.001 ng/kg/min and 0.01 ng/kg/min AVP increased gastric μHbO(2) to 87 ± 4% and 87 ± 6%, respectively, compared to baseline values (80 ± 7%), whereas application of 1 ng/kg/min AVP strongly reduced gastric μHbO(2) (59 ± 16%). V1A receptor blockade prior to AVP treatment abolished these effects on μHbO(2). 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). CONCLUSIONS: Exogenous AVP dose-dependently modulates gastric μHbO(2), with an increased μHbO(2) with ultra-low dose AVP. The effects of AVP on μHbO(2) are abolished by V1A receptor inhibition. These effects are independent of a modulation of systemic hemodynamic variables.