title: Indomethacin does not influence alveolar liquid clearance in anesthetized sheep or rats.
abstract: Active transport of sodium has been shown to be the predominant mechanism involved in alveolar liquid clearance. One regulatory mechanism involved in the modulation of this transport system is cAMP. Although it was initially thought that cAMP could directly modulate transepithelial Na+ transport, recent data suggest that this cAMP modulation could be secondary to the production of arachnidonic acid metabolites. The purpose of this study was thus to evaluate if prostaglandin products could have an indirect or direct role to play in lung liquid clearance. Addition of 10(-5) M salmeterol, known to increase intracellular cAMP, to the instilled fluid in rats stimulated lung liquid clearance. However, addition of indomethacin did not influence the stimulating effect of salmeterol. Furthermore, addition of prostaglandin E2 to the instilled fluid did not stimulate alveolar fluid clearance. In order to determine if this response could be species related, we evaluated if indomethacin could modulate alveolar liquid clearance in sheep. Presence of cAMP and aminophylline stimulated lung liquid clearance in sheep, but indomethacin did not inhibit this response. The present study demonstrates that cyclooxygenase products are not involved in the modulation of basal or stimulated alveolar or lung liquid clearance in sheep or rats.
authors.affiliation: Centre de recherche, CHUM, Montréal, Québec, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Berthiaume
authors.forename: H G
authors.initials: HG
authors.lastname: Folkesson
authors.forename: M A
authors.initials: MA
authors.lastname: Matthay
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D015633:Extravascular Lung Water / Q000187:drug effects* / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068299:Salmeterol Xinafoate; D012756:Sheep; D013045:Species Specificity
chemical_list: D000318:Adrenergic beta-Agonists; D016861:Cyclooxygenase Inhibitors; D011448:Prostaglandin Antagonists; D000068299:Salmeterol Xinafoate; D000242:Cyclic AMP; D015232:Dinoprostone; D000420:Albuterol; D007213:Indomethacin