The effect of alpha-adrenergic antagonism upon nitrogen loss during endotoxemia

Sixty male Sprague-Dawley rats were randomized to receive parenteral nutrition (PN) only; PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide (PN + LPS) at 6 mg.kg-1.d-1; or PN plus LPS plus a continuous infusion of the alpha-adrenergic antagonist phentolamine (PN + LPS + PHEN) at 5 mg.kg-1.d-1 or 20 mg.kg-1.d-1 for 48 h. All animals received isocaloric, isonitrogenous PN. LPS significantly lowered nitrogen balance (mmol/48 h) from PN control; however, addition of PHEN substantially worsened nitrogen balance compared with 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, respectively; P < 0.0001). Urinary 3-methylhistidine/creatinine ratio (3-meH/creat) 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-dose PHEN resulted in 82 +/- 9% blockade. To ascertain if any beneficial effect upon body protein loss is achieved during severe stress, 30 rats were given PN + LPS at 12 mg.kg-1.d-1 or PN + LPS12 + PHEN20. These data showed similar changes in nitrogen balance and 3-methylhistidine/creatinine with the use of PHEN during severe endotoxemia. alpha-adrenergic antagonism with PHEN worsens body protein loss as measured by nitrogen balance and 3-methylhistidine/creatinine in PN-fed endotoxemic rats.