Impairment of endothelial-dependent pulmonary vasorelaxation after mesenteric ischemia/reperfusion.
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.
Fullerton
D A
DA
Department of Surgery, University of Colorado, Denver, USA.
Eisenach
J H
JH
Friese
R S
RS
Agrafojo
J
J
Sheridan
B C
BC
McIntyre
R C
RC
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology / Q000473:pathology; D055370:Lung Injury; D008297:Male; D009504:Neutrophils / Q000473:pathology; D009599:Nitroprusside / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D013152:Splanchnic Circulation / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009599:Nitroprusside; D000001:Calcimycin; D009195:Peroxidase; D006152:Cyclic GMP; D000109:Acetylcholine