@article{13560634ea2b48f199eb7500f8c72b49,
title = "Impairment of endothelial-dependent pulmonary vasorelaxation after mesenteric ischemia/reperfusion",
abstract = "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- 6mol/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.",
author = "Fullerton, {D. A.} and Eisenach, {J. H.} and Friese, {R. S.} and J. Agrafojo and Sheridan, {B. C.} and Jr McIntyre",
note = "Funding Information: PULMONARY HYPERTENSION IS the major hemodynamic feature of acute lung injury. This pulmonary hypertension is derived from avid pulmonary vasoconstriction, at least early in the course of acute lung injury. 1 Net pulmonary vascular smooth muscle tone results from the mechanistic balance of vasoconstriction and vasorelax-ation. In the normal lung, basal endothelial release of the endogenous vasodilator nitric oxide (NO) contributes to the low pulmonary vascular smooth muscle tone. 2 Endothelial-derived NO lowers pulmonary vascular tone by stimulating guanylate cyclase in subjacent vascular smooth muscle cells to generate cyclic 3'-5' guanosine monophosphate (cGMP), which produces Supported by National Institutes of Health grant R29HL)t9398. Accepted for publication April 25, 1996. Reprint requests: David A. Fullerton, MD, Box C-310, University of Colorado Health Sciences Center, 4200 E. Ninth Ave., Denver, CO 80262. Copyright 9 1996 by Mosby-YearB ook, Inc. 0039-6060/96/$5.00 + 0 11/56/74501) pulmonary vascular smooth muscle relaxation.~ In acute lung injury, increased levels of circulating or local vasoconstricting agonists may contribute to increased pulmonary vascular tone. 4' 5 On the other hand, impairment of the mechanisms of pulmonary vasorelaxation in acute lung injury may contribute to pulmonary vasoconstriction by shifting net pulmonaryvascular smooth muscle tone in favor of vasoconstriction. The pulmo-nap/vasoconstriction seen in acute lung injury has been associated with histologic evidence of endothelial cell injury.6, 7 Therefore loss or deficiency of endothelial-derived NO in acute lung injury may help shift net pul-mona D , vascular smooth muscle tone in favor of vasoconstriction. In this way pulmonary vascular endothelial cell dysfunction may contribute to the pulmonary hypertension and pulmonary vasoconstriction seen in acute lung injury. Of note, cGMP-mediated pulmonary vasorelaxation is impaired in the rat in endotoxin-induced acute lung injury. 7 Mesenteric ischemia/reperfusion (I/R) is a common clinical cause of adult respiratory distress syndrome",
year = "1996",
doi = "10.1016/S0039-6060(96)80098-5",
language = "English (US)",
volume = "120",
pages = "879--884",
journal = "Surgery",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "5",
}