Intracellular mechanisms of pulmonary vasomotor dysfunction in acute lung injury caused by mesenteric ischemia-reperfusion.
BACKGROUND
A major hemodynamic feature of adult respiratory distress syndrome is pulmonary hypertension secondary to avid pulmonary vascular smooth muscle constriction. This study was undertaken to study the hypothesis that this pulmonary vasoconstriction may derive from pulmonary vasomotor dysfunction.


METHODS
A rat model of acute lung injury was studied after 2 hours of superior mesenteric arterial occlusion followed by 4 hours reperfusion. Lung neutrophil accumulation was assessed by myeloperoxidase assay, and lung leak was assessed by iodine 125-labeled albumin lung/blood ratio. The following mechanisms of pulmonary vascular smooth muscle relaxation were studied in isolated pulmonary arterial rings: (1) endothelial-dependent cyclic guanosine monophosphate-mediated, (2) endothelial-independent cyclic guanosine monophosphate-mediated, (3) beta-adrenergic cyclic adenosine monophosphate-mediated. Control rats underwent sham laparotomy. Statistical analysis was done with unpaired Student t test.


RESULTS
Lung myeloperoxidase increased from 6.2 +/- 2 to 42 +/- 5 units/gm (p < 0.05), and 125I-labeled albumin lung/blood ratio increased from 0.028 +/- 0.02 to 0.063 +/- 0.03 (p < 0.05) after mesenteric ischemia-reperfusion. beta-adrenergic cyclic adenosine monophosphate-mediated pulmonary vascular smooth muscle relaxation was dysfunctional in the lung-injured rats (62% +/- 5% relaxation versus 95% +/- 3% in controls) (p < 0.05).


CONCLUSIONS
These data suggest a mechanistic imbalance of pulmonary vascular smooth muscle contraction and relaxation in acute lung injury. Such imbalance may contribute to the pulmonary hypertension found in adult respiratory distress syndrome.
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262.
D A
DA
Fullerton
A R
AR
Hahn
K
K
Koike
A
A
Banerjee
A H
AH
Harken
D000208:Acute Disease; D000818:Animals; D008297:Male; D008641:Mesenteric Vascular Occlusion / Q000150:complications*; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D009504:Neutrophils / Q000502:physiology; D011651:Pulmonary Artery / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D015427:Reperfusion Injury / Q000150:complications*; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000503:physiopathology*; D014661:Vasoconstriction; D014664:Vasodilation
D011943:Receptors, Adrenergic, beta