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• W2158454940 abstract "BackgroundThe roles of arachidonic acid (AA) metabolites in hypoxia-induced pulmonary vasoconstriction (HPV), a critical physiological mechanism that prevents ventilation/perfusion mismatch, are still incompletely understood.MethodsPulmonary arterial pressure was measured in ventilated/perfused rat lungs. Isometric tones of rat intralobar pulmonary arteries were also measured, using a myograph.ResultsHypoxia (Po2, 3%)-induced pulmonary arterial pressure increases (ΔPAPhypox) were stable with blood-mixed perfusate, but decayed spontaneously. ΔPAPhypox was inhibited by 29%, 16%, and 28% by the thromboxane A2 (TXA2) antagonist SQ-29548, the 5-lipoxygenase inhibitor, MK886, and the leukotriene D4 antagonist, LY-171883, respectively. The prostacyclin synthase inhibitor tranylcypromine augmented ΔPAPhypox by 5%, whereas inhibition of cytochrome P450 did not affect ΔPAPhypox. Consistently, the TXA2 analogue U46619 increased ΔPAPhypox whereas prostacyclin abolished ΔPAPhypox. However, leukotriene D4 had no direct effect on ΔPAPhypox. In the isolated pulmonary arteries, pretreatment with U46619 was essential to demonstrate hypoxia-induced contraction.ConclusionsThe above results suggest that TXA2 and cysteinyl leukotrienes, other than leukotriene D4, are endogenous factors that facilitate HPV in rats. The indispensable role of TXA2-induced pretone in the HPV of isolated pulmonary arteries indicates that the signal from thromboxane receptors might be a critical component of oxygen sensation mechanisms." @default.
• W2158454940 created "2016-06-24" @default.
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• W2158454940 date "2011-01-01" @default.
• W2158454940 modified "2023-10-15" @default.
• W2158454940 title "Role of arachidonic acid-derived metabolites in the control of pulmonary arterial pressure and hypoxic pulmonary vasoconstriction in rats" @default.
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• W2158454940 doi "https://doi.org/10.1093/bja/aeq268" @default.
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