title: Arachidonic acid metabolites and an early stage of pulmonary hypertension in chronically hypoxic newborn pigs.
abstract: Our purpose was to determine whether production of arachidonic acid metabolites, particularly cyclooxygenase (COX) metabolites, is altered in 100-400-microm-diameter pulmonary arteries of piglets at an early stage of pulmonary hypertension. Piglets were raised in either room air (control) or hypoxia for 3 days. A cannulated artery technique was used to measure responses of 100-400-microm-diameter pulmonary arteries to arachidonic acid, a prostacyclin analog, or the thromboxane mimetic. Radioimmunoassay was used to determine pulmonary artery production of thromboxane B(2) (TxB(2)) and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), the stable metabolites of thromboxane and prostacyclin, respectively. Assessment of abundances of COX pathway enzymes in pulmonary arteries was determined by immunoblot technique. Arachidonic acid induced less dilation in pulmonary arteries from hypoxic than in pulmonary arteries from control piglets. Pulmonary artery responses to prostacyclin and were similar for both groups. 6-Keto-PGF(1alpha) production was reduced, whereas TxB(2) production was increased in pulmonary arteries from hypoxic piglets. Abundances of both COX-1 and prostacyclin synthase were reduced, whereas abundances of both COX-2 and thromboxane synthase were unaltered in pulmonary arteries from hypoxic piglets. At least partly due to altered abundances of COX pathway enzymes, a shift in production of arachidonic acid metabolites, away from dilators toward constrictors, may contribute to the early phase of chronic hypoxia-induced pulmonary hypertension in newborn piglets.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. cfike@wfubmc.edu
authors.forename: Candice D
authors.initials: CD
authors.lastname: Fike
authors.forename: Mark R
authors.initials: MR
authors.lastname: Kaplowitz
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Pfister
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D015121:6-Ketoprostaglandin F1 alpha / Q000037:antagonists & inhibitors; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D002908:Chronic Disease; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications*; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D011451:Prostaglandin-Endoperoxide Synthases; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values; D013552:Swine; D013929:Thromboxane B2 / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000378:metabolism
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003577:Cytochrome P-450 Enzyme System; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase