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Impairment of endothelial-dependent pulmonary vasorelaxation after mesenteric ischemia/reperfusion
D A Fullerton1, J H Eisenach, R S Friese
1Department of Surgery, University of Colorado, Denver, USA.
Background:
A major hemodynamic feature of acute lung injury is pulmonary hypertension caused by pulmonary vasoconstriction. Impairment of the mechanisms of pulmonary vasorelaxation may contribute to this pulmonary vasoconstriction. This study examined the effect of mesenteric ischemia/reperfusion (I/R) on lung neutrophil accumulation and endothelial-dependent and -independent cyclic 3'-5' guanosine monophosphate-mediated pulmonary vasorelaxation in rats.
Methods:
Rats were studied after 1 hour of superior mesenteric artery occlusion and 2 hours of reperfusion. Lung neutrophil accumulation was determined by myeloperoxidase assay (MPO). The following mechanisms of pulmonary vasorelaxation were studied in isolated pulmonary artery rings by generating dose response curves (10(-9) to 10(-6)mol/L): (1) receptor-dependent, endothelial-dependent relaxation (response to acetylcholine), (2) receptor-independent, endothelial-dependent relaxation (response to the calcium ionophore, A23187), and (3) endothelial-independent relaxation (response to sodium nitroprusside [SNP]).
Results:
Lung MPO activity was significantly increased from 2.4 +/- 0.2 units/gm lung weight in controls to 10.3 +/- 0.4 after mesenteric I/R (p < 0.05). The vasorelaxation response to SNP was not different after mesenteric I/R, but vasorelaxation by both acetylcholine and A23187 were significantly impaired.
Conclusions:
Endothelial-dependent pulmonary vasorelaxation is significantly impaired after mesenteric I/R. Such impairment of pulmonary vasorelaxation may help tip the net balance of pulmonary vasomotor tone toward vasoconstriction and contribute to the pulmonary hypertension seen in acute lung injury.
Insights
Mesenteric ischemia/reperfusion impairs endothelial-dependent pulmonary vasorelaxation in rats. This dysfunction may contribute to pulmonary hypertension in acute lung injury by favoring vasoconstriction.
Area of Science:
- Cardiovascular Physiology
- Pulmonary Medicine
- Surgical Injury Models
Background:
- Acute lung injury is characterized by pulmonary hypertension due to vasoconstriction.
- Impaired pulmonary vasorelaxation mechanisms may exacerbate this vasoconstriction.
- Mesenteric ischemia/reperfusion (I/R) is investigated for its impact on lung function.
Purpose of the Study:
- To assess the effect of mesenteric I/R on lung neutrophil accumulation.
- To evaluate endothelial-dependent and -independent pulmonary vasorelaxation.
- To determine the role of cyclic 3'-5' guanosine monophosphate (cGMP) in these responses.
Main Methods:
- Rats underwent 1-hour mesenteric artery occlusion followed by 2-hour reperfusion.
- Lung neutrophil accumulation was quantified using myeloperoxidase (MPO) assay.
- Pulmonary artery ring relaxation responses to acetylcholine, A23187, and sodium nitroprusside (SNP) were measured.
Main Results:
- Mesenteric I/R significantly increased lung MPO activity.
- Vasorelaxation to SNP remained unchanged post-I/R.
- Endothelial-dependent vasorelaxation, induced by acetylcholine and A23187, was significantly impaired.
Conclusions:
- Mesenteric I/R significantly impairs endothelial-dependent pulmonary vasorelaxation.
- This impairment may shift pulmonary vasomotor tone towards vasoconstriction.
- Such a shift could contribute to the pulmonary hypertension observed in acute lung injury.