enalaprilat-anhydrous and Shock

Topics: Animals; Burns; Disease Models, Animal; Enalaprilat; Humans; Hypoxia; Mitogen-Activated Protein Kinases; Nitric Oxide Synthase; Protoporphyrins; Sepsis; Shock

Sympathetic and angiotensinergic activation reduce splanchnic oxygen delivery during hypovolemia, which may lead to failure of the intestinal mucosal barrier and eventually multiple organ dysfunction. This study integrates sympathetic and angiotensinergic responses with splanchnic hemodynamics and duodenal mucosal function during hypovolemia and evaluates pharmacologic blockade of either system to ameliorate the impact of acute hypovolemia. Chloralose-anesthetized pigs subjected to 20 and 40% blood volume reductions were randomized to controls or administered guanethidine or enalaprilate to block sympathetic and angiotensinergic activation, as assessed by plasma norepinephrine spillover and angiotensin II levels, respectively. Mesenteric and hepatic oxygen delivery/consumption as well as duodenal mucosal alkaline secretion and potential difference were determined. Hypovolemia preferentially increased mesenteric sympathetic outflow and caused a vigorous angiotensinergic activation. Guanethidine and enalaprilate blocked effectively the sympathetic and angiotensinergic responses. Treatment with enalaprilate, but not guanethidine, prevented the reduction of mesenteric oxygenation and duodenal mucosal alkaline secretion and potential difference observed in control animals. The down-regulation of mesenteric oxygenation and duodenal mucosal function during hypovolemia can be prevented by administration of enalaprilate, whereas guanethidine is uneffective in this respect. Interference with the reninangiotensin system might be of clinical interest to support mesenteric perfusion and organ function in hypovolemia.

Topics: Angiotensin II; Animals; Bicarbonates; Duodenum; Enalaprilat; Guanethidine; Hemodynamics; Intestinal Mucosa; Membrane Potentials; Multiple Organ Failure; Norepinephrine; Renin-Angiotensin System; Shock; Splanchnic Circulation; Swine; Sympathetic Nervous System; Sympatholytics