ENDOTOXIN DIFFERENTIALLY IMPAIRS CYCLIC GUANOSINE MONOPHOSPHATE-MEDIATED RELAXATION IN THE PULMONARY AND SYSTEMIC CIRCULATIONS

Objectives: The purpose of this study was to determine the effect of e ndotoxin on alpha(1)-adrenergic receptor vasoconstriction and both end othelium-dependent and -independent cyclic guanosine monophosphate (cG MP)-mediated vasodilation in the pulmonary and systemic circulations. Design: Prospective, multiple group, controlled experimental study. Se tting: Medical school research laboratory. Subjects: Male Sprague-Dawl ey rats, weighing 250 to 350 g. Interventions: Six hours after endotox in (20 mg/kg intraperitoneally) or saline, the response to the a) alph a(1)-adrenergic receptor agonist, phenylephrine; b) endothelium-depend ent vasodilator, acetylcholine; and c) the endothelium-independent vas odilator, sodium nitroprusside, was determined in isolated rat pulmona ry artery and thoracic aortic rings. Measurements and Main Results: En dotoxin caused a significant decrease in the response to phenylephrine in the aorta but did not affect the response in the pulmonary artery. Endotoxin caused significant impairment of relaxation to acetylcholin e and sodium nitroprusside in the pulmonary circulation. In central ri ngs, only 4 +/- 1% of the preconstricted tension remained in response to acetylcholine vs. 77 +/- 3% following endotoxin administration (p < .05). Similarly, sodium nitroprusside resulted in complete pulmonary r ing relaxation in controls vs. 18 +/- 3% tension remaining following e ndotoxin administration (p <.05). On the other hand, only the response to acetylcholine was dysfunctional in the thoracic aorta. In thoracic aortic rings from control rats, acetylcholine caused complete relaxat ion; however, 23 +/- 5% of the preconstricted tension remained followi ng endotoxin administration. The response to sodium nitroprusside in t he thoracic aorta from endotoxin-treated rats was not different from c ontrol. Conclusions: From these data, we conclude that endotoxin cause s organ-specific changes in vascular reactivity. These changes in vasc ular reactivity favor a decrease in vascular pressure and resistance i n the systemic circulation, and an increase in vascular pressure and r esistance in the pulmonary circulation in response to endotoxin.