No redistribution of lung blood flow by inhaled nitric oxide in endotoxemic piglets pretreated with an endothelin receptor antagonist
2015 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 118, no 6, 768-775 p.Article in journal (Refereed) Published
Inhaled nitric oxide (INO) improves ventilation-perfusion matching and alleviates pulmonary hypertension in patients with acute respiratory distress syndrome. However, outcome has not yet been shown to improve, and non-response is common. A better understanding of the mechanisms by which INO acts, may guide in improving treatment with INO in patients with severe respiratory failure. We hypothesized that INO may act not only by vasodilation in ventilated lung regions, but also by causing vasoconstriction via endothelin (ET-1) in atelectatic, non-ventilated lung regions. This was studied in 30 anesthetized, mechanically ventilated piglets. The fall in oxygenation and rise in pulmonary artery pressure during a sepsis-like condition (infusion of endotoxin) were blunted by INO 40ppm. Endotoxin infusion increased serum ET-1, and INO almost doubled the ratio between mRNA expression of endothelin receptor A (mediating vasoconstriction) and B (mediating vasodilation and clearance of ET-1) (ET-A/ET-B) in atelectatic lung regions. INO caused a shift in blood flow away from atelectatic lung regions in the endotoxemic piglets, but not during ET receptor antagonism. We conclude that INO in short term experiments, in addition to causing selective pulmonary vasodilation in ventilated lung regions, also increases the ET-A/ET-B mRNA expression ratio in lung tissue. This might augment the vasoconstriction in atelectatic lung regions, enhancing the redistribution of pulmonary blood flow to ventilated lung regions which are reached by INO. Such vasoconstriction may be an important additional factor explaining the effect of INO.
Place, publisher, year, edition, pages
2015. Vol. 118, no 6, 768-775 p.
Clinical Medicine Physiology
IdentifiersURN: urn:nbn:se:uu:diva-243210DOI: 10.1152/japplphysiol.00591.2014ISI: 000350985100014PubMedID: 25549764OAI: oai:DiVA.org:uu-243210DiVA: diva2:786406