Hypercapnia (HC) increases systemic oxygen delivery (DO₂) and gastric mucosal oxygenation. However, it activates the renin–angiotensin–aldosterone system (RAAS), which conversely reduces mesenteric perfusion. The aims of this study were to evaluate the effect of RAAS inhibition during normocapnia and HC on oral and gastric mucosal oxygenation (μHbO₂) and to assess the effect of blood pressure under these circumstances. Five dogs were repeatedly anesthetized to study the effects of ACE inhibition (ACE-I; 5 mg/kg captopril, followed by 0.25 mg/kg per h) on μHbO₂ (reflectance spectrophotometry) and hemodynamic variables during normocapnia (end-tidal CO₂=35 mmHg) and HC (end-expiratory carbon dioxide (etCO₂)=70 mmHg). In the control group, the dogs were subjected to HC alone. To exclude the effects of reduced blood pressure, in one group, blood pressure was maintained at baseline values via titrated phenylephrine (PHE) infusion during HC and additional captopril infusion. ACE-I strongly reduced gastric μHbO₂ from 72±2 to 65±2% and mean arterial pressure (MAP) from 64±2 to 48±4 mmHg, while DO₂ remained unchanged. This effect was counteracted in the presence of HC, which increased gastric μHbO₂ from 73±3 to 79±6% and DO₂ from 15±2 to 22±4 ml/kg per min during ACE-I without differences during HC alone. However, MAP decreased similar to that observed during ACE-I alone from 66±3 to 47±5 mmHg, while left ventricular contractility (dP_max) increased from 492±63 to 758±119 mmHg/s. Titrated infusion of PHE had no additional effects on μHbO₂. In summary, our data suggest that RAAS inhibition reduces gastric mucosal oxygenation in healthy dogs. HC not only abolishes this effect, but also increases μHbO₂, DO₂, and dP_max. The increase in μHbO₂ during ACE-I under HC is in accordance with our results independent of blood pressure.

Hypercapnia (HC) improves systemic oxygen delivery (DO₂) and microvascular hemoglobin oxygenation of the mucosa (μHbO₂). Simultaneously, HC increases plasma levels of vasopressin. Although vasopressin is generally regarded a potent vasoconstrictor particularly in the splanchnic region, its effects on splanchnic microcirculation during HC is unclear. The aim of this study was to evaluate the role of endogenous vasopressin on gastric mucosal oxygenation and hemodynamic variables during physiological (normocapnia) and hypercapnic conditions. Five dogs were repeatedly anesthetized to study the effect of vasopressin V_1A receptor blockade ([Pmp¹,Tyr(Me)²]-Arg⁸-Vasopressin, 35 μg/kg) on hemodynamic variables and μHbO₂ during normocapnia or HC (end-tidal CO₂ 70 mmHg). In a control group, animals were subjected to HC alone. μHbO₂ was measured by reflectance spectrophotometry, systemic DO₂ was calculated from intermittent blood gas analysis, and cardiac output was measured by transpulmonary thermodilution. Data are presented as mean±s.e.m. for n=5 animals. During HC alone, DO₂ increased from 12±1 to 16±1 ml/kg per min and μHbO₂ from 70±4 to 80±2%. By contrast, additional vasopressin V_1A receptor blockade abolished the increase in μHbO₂ (80±2 vs 69±2%) without altering the increase in DO₂ (16±1 vs 19±2 ml/kg per min). Vasopressin V_1A receptor blockade (VB) during normocapnia neither affected DO₂ (13±1 vs 14±1 ml/kg per min) nor μHbO₂ (75±3 vs 71±5%). Vasopressin V_1A receptor blockade abolished the increase in μHbO₂ during HC independent of DO₂. Thus, in contrast to its generally vasoconstrictive properties, the vasopressin V_1A receptors seem to mediate the increase in gastric microcirculatory mucosal oxygenation induced by acute HC.

During circulatory shock, gastrointestinal microcirculation is impaired, especially via activation of the renin-angiotensin-aldosterone system. Therefore, inhibition of the renin-angiotensin-aldosterone system might be beneficial in maintaining splanchnic microcirculation. The aim of this study was to analyze whether locally applied losartan influences gastric mucosal perfusion (µflow, µvelo) and oxygenation (µHbO₂) without systemic hemodynamic changes. In repetitive experiments six anesthetized dogs received 30 mg losartan topically on the oral and gastric mucosa during normovolemia and hemorrhage (−20% blood volume). Microcirculatory variables were measured with reflectance spectrometry, laser Doppler flowmetry and incident dark field imaging. Transpulmonary thermodilution and pulse contour analysis were used to measure systemic hemodynamic variables. Gastric barrier function was assessed via differential absorption of inert sugars. During normovolemia, losartan increased gastric µflow from 99 ± 6 aU to 147 ± 17 aU and µvelo from 17 ± 1 aU to 19 ± 1 aU. During hemorrhage, losartan did not improve µflow. µvelo decreased from 17 ± 1 aU to 14 ± 1 aU in the control group. Application of losartan did not significantly alter µvelo (16 ± 1 aU) compared to the control group and to baseline levels (17 ± 1 aU). No effects of topical losartan on macrohemodynamic variables or microcirculatory oxygenation were detected. Gastric microcirculatory perfusion is at least partly regulated by local angiotensin receptors. Topical application of losartan improves local perfusion via vasodilation without significant effects on systemic hemodynamics. During mild hemorrhage losartan had minor effects on regional perfusion, probably because of a pronounced upstream vasoconstriction.