THE EFFECT OF ALPHA-ADRENERGIC ANTAGONISM UPON NITROGEN LOSS DURING ENDOTOXEMIA

Sixty male Sprague-Dawley rats were randomized to receive parenteral n utrition (PN) only; PN plus continuous infusion of Escherichia coil 02 6:B6 lipopolysaccharide (PN + LPS) at 6 mg.kg(-1).d(-1); or PN plus LP S plus a continuous infusion of the alpha-adrenergic antagonist phento lamine (PN + LPS + PHEN) at 5 mg.kg(-1).d(-1) or 20 mg.kg(-1).d(-1) fo r 48 h. All animals received isocaloric, isonitrogenous PN. LPS signif icantly lowered nitrogen balance (mmol/48 h) from PN control; however, addition of PHEN substantially worsened nitrogen balance compared wit h LPS (14.2 +/- 3, 2.4 +/- 5.2, -1.6 +/- 4.5, -0.8 +/- 5.4, for the PN , PN + LPS, PN + LPS + PHEN5 and PN + LPS + PHEN20 groups, respectivel y; P < 0.0001). Urinary 3-methylhistidine/creatinine ratio (3-meH/crea t) paralleled the nitrogen balance data (0.30 +/- 0.09, 0.45 +/- 0.12, 0.51 +/- 0.14, 0.60 +/- 0.12, respectively; P < 0.0001). The high-dos e PHEN resulted in 82 +/- 9% blockade. To ascertain if any beneficial effect upon body protein loss is achieved during severe stress, 30 rat s were given PN + LPS at 12 mg.kg(-1).d(-1) or PN + LPS12 + PHEN20. Th ese data showed similar changes in nitrogen balance and 3-methyhistidi ne/creatinine with the use of PHEN during severe endotoxemia. alpha-ad renergic antagonism with PHEN worsens body protein loss as measured by nitrogen balance and 3-methylhistadine/creatinine in PN-fed endotoxem ic rats. (C) Elsevier Science Inc, 1997.