Effect of Sustained Endotoxemia on α1‐Adrenergic Responsiveness in Parenterally Fed Rats

Abstract

We investigated the effect of endotoxemia on α1‐adrenergic receptor‐mediated smooth muscle contraction as measured by mean arterial pressure (MAP) in response to incremental doses of a vasopressor. Twelve male Sprague‐Dawley rats were randomized to receive parenteral nutrition alone (PN) or in combination with a continuous infusion of endotoxin (PN‐LPS) for 48 hours. Incremental doses of phenylephrine were given and peak MAP response was recorded. The endotoxin group had a decreased rise in MAP with the same dose of phenylephrine compared with the control group (59 ± 14 and 99 ± 12 mm Hg, respectively, p<0.001). However, the baseline MAP was higher in the endotoxin group (102 ± 18 and 71 ± 7 mm Hg, respectively, p<0.002). The overall maximum effect was the same for both groups (161 ± 16 and 170 ± 8 mm Hg, respectively, p=NS). These data indicate that sustained endotoxemia does not result in desensitization of α1‐adrenergic responsiveness. Other mechanisms are responsible for the ineffectiveness of vasopressors during advanced sepsis.