Inhaled nitric oxide prevents pulmonary endothelial dysfunction after mesenteric ischemia-reperfusion.
This study examined the effect of inhaled nitric oxide (NO) on lung neutrophil accumulation and endothelial-dependent and -independent guanosine 3',5'-cyclic monophosphate (cGMP)-mediated mechanisms of pulmonary vasorelaxation after mesenteric ischemia-reperfusion (I/R) in mechanically ventilated rats. Inhaled NO (20 ppm) was administered in two protocols: 1) throughout mesenteric I/R and 2) during mesenteric reperfusion alone. Concentration-response curves were generated (10(-9) to 10(-8) M) for acetylcho-line (ACh), A23187, and sodium nitroprusside (SNP) in isolated pulmonary arterial rings preconstricted with phenylephrine. Lung neutrophil accumulation [myeloperoxidase assay (MPO)] was significantly increased from 2.4 +/- 0.2 units/g lung wt in controls to 10.3 +/- 0.4 after 1 h of superior mesenteric artery occlusion and 2 h of reperfusion. Lung MPO activity was not different from controls in rats receiving inhaled NO either 1) during mesenteric I/R or during mesenteric reperfusion alone. The concentration-response curves demonstrated significant impairment of pulmonary vasorelaxation by endothelial-dependent mechanisms (response to ACh and A23187) but not endothelial-independent pulmonary vasorelaxation (response to SNP) after mesenteric I/R. This pulmonary vasomotor dysfunction was prevented by administration of inhaled NO during either mesenteric I/R or during mesenteric reperfusion alone. We conclude that inhaled NO prevents lung neutrophil accumulation and pulmonary vascular endothelial dysfunction after mesenteric I/R.
Fullerton
D A
DA
University of Colorado Health Sciences Center, Denver 80262, USA.
Eisenach
J H
JH
McIntyre
R C
RC
Friese
R S
RS
Sheridan
B C
BC
Roe
G B
GB
Agrafojo
J
J
Banerjee
A
A
Harken
A H
AH
D000280:Administration, Inhalation; D000818:Animals; D001794:Blood Pressure; D000242:Cyclic AMP / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D007511:Ischemia / Q000503:physiopathology*; D008168:Lung / Q000473:pathology; D008297:Male; D008643:Mesentery / Q000098:blood supply*; D009504:Neutrophils / Q000473:pathology; D009569:Nitric Oxide / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D014664:Vasodilation / Q000502:physiology
D009569:Nitric Oxide; D000242:Cyclic AMP