EFFECT OF SUSTAINED ENDOTOXEMIA ON ALPHA(1)-ADRENERGIC RESPONSIVENESSIN PARENTERALLY FED RATS

We investigated the effect of endotoxemia on alpha(1)-adrenergic recep tor-mediated smooth muscle contraction as measured by mean arterial pr essure (MAP) in response to incremental doses of a vasopressor; Twelve male Sprague-Dawley rats were randomized to receive parenteral nutrit ion alone (PN) or in combination with a continuous infusion of endotox in (PN-LPS) for 48 hours. Incremental doses of phenylephrine were give n and peak MAP response was recorded. The endotoxin group had a decrea sed 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 +/- 1 8 and 71 +/- 7 mm Hg, respectively, p<0.002). The overall maximum effe ct was the same for both groups (161 +/- 16 and 170 +/- 8 mm Hg, respe ctively, p=NS). These data indicate that sustained endotoxemia does no t result in desensitization of alpha(1)-adrenergic responsiveness. Oth er mechanisms are responsible for the ineffectiveness of vasopressors during advanced sepsis.