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Effect of Sustained Endotoxemia on α 1 ‐Adrenergic Responsiveness in Parenterally Fed Rats
Author(s) -
Dickerson Roland N.,
Lima John J.,
Kuhl David A.,
Brown Rex O.,
Hak Lawrence J.
Publication year - 1998
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1998.tb03835.x
Subject(s) - phenylephrine , medicine , contraction (grammar) , mean arterial pressure , desensitization (medicine) , adrenergic , sepsis , endocrinology , adrenergic receptor , anesthesia , blood pressure , receptor , heart rate
We investigated the effect of endotoxemia on α 1 ‐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 α 1 ‐adrenergic responsiveness. Other mechanisms are responsible for the ineffectiveness of vasopressors during advanced sepsis.