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Hemodynamic and metabolic effects of vasopressin blockade in endotoxin shock
1Department of Surgery, University of California, Davis, Sacramento 95817-2282, USA.
Background:
Arginine vasopressin V1 receptor antagonist (AVPRA) was administered to investigate the influence of vasopressin blockade on hemodynamics and metabolism during endotoxin shock.
Methods:
Anesthetized rats were divided into four groups: control (0.9% saline solution, n = 5), drug control (AVPRA, n = 5), endotoxin (endotoxin, 5 mg/kg, n = 10), and pretreatment (AVPRA and endotoxin, n = 10). Hemodynamics and oxygen transport were evaluated for 2 hours. Terminal arterial and portal venous concentrations of endotoxin, pyruvate, lactate, and ketone bodies were determined.
Results:
The endotoxin group maintained blood pressure levels similar to those of control animals. AVPRA pretreatment decreased vascular resistance and resulted in lower blood pressure than endotoxin alone. Endotoxin decreased oxygen consumption and the oxygen extraction ratio and increased arterial lactate concentration and the lactate/pyruvate ratio. Endotoxin also decreased arterial ketone body concentration and markedly decreased ketone body availability in the mesenteric circulation. AVPRA pretreatment improved oxygen consumption, oxygen extraction ratio, and ketone body availability; arterial lactate concentration, lactate/pyruvate ratio, and arterial ketone body concentration were not affected. Pretreatment with AVPRA also decreased arterial and portal venous concentrations of endotoxin.
Conclusions:
Vasopressin receptor blockade during endotoxemia resulted in lower blood pressure than endotoxin alone. Vasopressin receptor blockade also maintained oxygen extraction ratio and ketone body availability in the mesenteric circulation. Vasopressin may play a key role in the response to endotoxemia.