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 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.

[1]  R. McIntyre,et al.  Inhaled nitric oxide variably improves oxygenation and pulmonary hypertension in patients with acute respiratory distress syndrome. , 1995, The Journal of trauma.

[2]  W. Graier,et al.  Escherichia coli endotoxin inhibits agonist-mediated cytosolic Ca2+ mobilization and nitric oxide biosynthesis in cultured endothelial cells. , 1994, Circulation research.

[3]  R. McIntyre,et al.  Mechanisms of pulmonary vascular control in normal and injured lungs. , 1994, Surgery.

[4]  J. Bertrand,et al.  Effects of Nitric Oxide (No) in Ards Patients Seem Unpredictable , 1994 .

[5]  K. Albertine,et al.  Loss of endothelium-dependent vasodilation in the pulmonary vessels of sheep after prolonged endotoxin. , 1994, Journal of applied physiology.

[6]  W. Sibbald,et al.  Differential impairment of vascular reactivity of small pulmonary and systemic arteries in hyperdynamic sepsis. , 1993, The American review of respiratory disease.

[7]  J. Parrillo.  Pathogenetic mechanisms of septic shock. , 1993, The New England journal of medicine.

[8]  H. Adams,et al.  Selective inhibition of endothelium-dependent vasodilator capacity by Escherichia coli endotoxemia. , 1993, Circulation research.

[9]  S. Peters,et al.  A multicenter registry of patients with acute respiratory distress syndrome. Physiology and outcome. , 1992, The American review of respiratory disease.

[10]  R. Winquist,et al.  Regional differences in the effects of septic shock on vascular reactivity in the rabbit. , 1992, The Journal of pharmacology and experimental therapeutics.

[11]  E. Rackow,et al.  Pathophysiology and treatment of septic shock. , 1991, JAMA.

[12]  P. Schumacker,et al.  Endotoxin in vivo impairs endothelium-dependent relaxation of canine arteries in vitro. , 1990, The American review of respiratory disease.

[13]  T. Mckenna,et al.  Prolonged exposure of rat aorta to low levels of endotoxin in vitro results in impaired contractility. Association with vascular cytokine release. , 1990, The Journal of clinical investigation.

[14]  R. Bone,et al.  Clinical Investigations in Critical CareRandomized Double-Blind, Multicenter Study of Prostaglandin E1 in Patients with the Adult Respiratory Distress Syndrome , 1989 .

[15]  I. Wakabayashi,et al.  Diminution of contractile response of the aorta from endotoxin-injected rats. , 1987, European journal of pharmacology.

[16]  N. Voelkel,et al.  Platelet-activating factor mediates hemodynamic changes and lung injury in endotoxin-treated rats. , 1987, The Journal of clinical investigation.

[17]  L. Homer,et al.  Diminished pressor response to exogenous norepinephrine and angiotensin II in septic, unanesthetized rats: evidence for a prostaglandin-mediated effect. , 1985, The Journal of surgical research.

[18]  B. Meyrick,et al.  Acute effects of Escherichia coli endotoxin on the pulmonary microcirculation of anesthetized sheep structure:function relationships. , 1983, Laboratory investigation; a journal of technical methods and pathology.

[19]  A. Fein,et al.  The risk factors, incidence, and prognosis of ARDS following septicemia. , 1983, Chest.

[20]  P. Pepe,et al.  Clinical predictors of the adult respiratory distress syndrome. , 1982, American journal of surgery.

[21]  F. Lewis,et al.  Cardiopulmonary parameters and prognosis after severe multiple trauma. , 1979, The Journal of trauma.

[22]  W. Zapol,et al.  Pulmonary hypertension in severe acute respiratory failure. , 1977, The New England journal of medicine.