SYMPATHETIC AND RENIN-ANGIOTENSIN ACTIVATION DURING GRADED HYPOVOLEMIA IN PIGS - IMPACT ON MESENTERIC PERFUSION AND DUODENAL MUCOSAL FUNCTION

Sympathetic and angiotensinergic activation reduce splanchnic oxygen d elivery during hypovolemia, which may lead to failure of the intestina l mucosal barrier and eventually multiple organ dysfunction. This stud y integrates sympathetic and angiotensinergic responses with splanchni c hemodynamics and duodenal mucosal function during hypovolemia and ev aluates pharmacologic blockade of either system to ameliorate the impa ct of acute hypovolemia. Chloralose-anesthetized pigs subjected to 20 and 40% blood volume reductions were randomized to controls or adminis tered guanethidine or enalaprilate to block sympathetic and angiotensi nergic activation, as assessed by plasma norepinephrine spillover and angiotensin II levels, respectively. Mesenteric and hepatic oxygen del ivery/consumption as well as duodenal mucosal alkaline secretion and p otential difference were determined. Hypovolemia preferentially increa sed mesenteric sympathetic outflow and caused a vigorous angiotensiner gic activation. Guanethidine and enalaprilate blocked effectively the sympathetic and angiotensinergic responses. Treatment with enalaprilat e, but not guanethidine, prevented the reduction of mesenteric oxygena tion and duodenal mucosal alkaline secretion and potential difference observed in control animals. The down-regulation of mesenteric oxygena tion and duodenal mucosal function during hypovolemia can be prevented by administration of enalaprilate, whereas guanethidine is uneffectiv e in this respect. Interference with the renin-angiotensin system migh t be of clinical interest to support mesenteric perfusion and organ fu nction in hypovolemia.