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BJA: British Journal of Anaesthesia
Year: 2011  |  Volume: 106  |  Issue: 1  |  Page No.: 31 - 37

Role of arachidonic acid-derived metabolites in the control of pulmonary arterial pressure and hypoxic pulmonary vasoconstriction in rats

S. J Park, H. Y Yoo, Y. E Earm, S. J Kim, J. K Kim and S. D. Kim    

Abstract: Background

The 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.

Methods

Pulmonary arterial pressure was measured in ventilated/perfused rat lungs. Isometric tones of rat intralobar pulmonary arteries were also measured, using a myograph.

Results

Hypoxia (Po2, 3%)-induced pulmonary arterial pressure increases (PAPhypox) were stable with blood-mixed perfusate, but decayed spontaneously. PAPhypox 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 PAPhypox by 5%, whereas inhibition of cytochrome P450 did not affect PAPhypox. Consistently, the TXA2 analogue U46619 increased PAPhypox whereas prostacyclin abolished PAPhypox. However, leukotriene D4 had no direct effect on PAPhypox. In the isolated pulmonary arteries, pretreatment with U46619 was essential to demonstrate hypoxia-induced contraction.

Conclusions

The 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.

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