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Endotoxin differentially impairs cyclic guanosine monophosphate-mediated relaxation in the pulmonary and systemic
R C McIntyre1, B Sheridan, J Agrafojo
1Department of Surgery, University of Colorado Health Sciences Center, Denver, USA.
Objectives:
The purpose of this study was to determine the effect of endotoxin on alpha1-adrenergic receptor vasoconstriction and both endothelium-dependent and -independent cyclic guanosine monophosphate (cGMP)-mediated vasodilation in the pulmonary and systemic circulations.
Design:
Prospective, multiple group, controlled experimental study.
Setting:
Medical school research laboratory.
Subjects:
Male Sprague-Dawley rats, weighing 250 to 350 g.
Interventions:
Six hours after endotoxin (20 mg/kg intraperitoneally) or saline, the response to the a) alpha1-adrenergic receptor agonist, phenylephrine; b) endothelium-dependent vasodilator, acetylcholine; and c) the endothelium-independent vasodilator, sodium nitroprusside, was determined in isolated rat pulmonary artery and thoracic aortic rings.
Measurements And Main Results:
Endotoxin 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 acetylcholine and sodium nitroprusside in the pulmonary circulation. In control rings, 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 ring relaxation in controls vs. 18 +/- 3% tension remaining following endotoxin 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 relaxation; however, 23 +/- 5% of the preconstricted tension remained following endotoxin administration. The response to sodium nitroprusside in the thoracic aorta from endotoxin-treated rats was not different from control.
Conclusions:
From these data, we conclude that endotoxin causes organ-specific changes in vascular reactivity. These changes in vascular reactivity favor a decrease in vascular pressure and resistance in the systemic circulation, and an increase in vascular pressure and resistance in the pulmonary circulation in response to endotoxin.