Korean J Anesthesiol.  2009 Oct;57(4):472-482. 10.4097/kjae.2009.57.4.472.

Effects of ATP and LTC4 on hypoxic pulmonary vasoconstriction in isolated rat lungs

• Rho JY
• Shin HY
• Kim HC
• Lee JW
• Kim SD

• KMID: 1765452
• DOI: http://doi.org/10.4097/kjae.2009.57.4.472

Abstract

BACKGROUND
Hypoxic pulmonary vasoconstriction (HPV) is unique to pulmonary circulation but the mechanism remains elusive. Red blood cells (RBCs) are known to augment HPV and to release more ATP as oxygen content falls. Leukotrienes constrict smooth muscle and could be important for the regulation of the pulmonary circulation. Hence we hypothesized that ATP and leukotrienes are mediators of HPV produced during acute alveolar hypoxia.
METHODS
In forty Sprague-Dawley rats, lungs were isolated and perfused. We administered ATP (10 micrometer) to the ATP group (n = 8), the ATP antagonist, suramin (100 micrometer) to the suramin group (n = 8), leukotriene C4 (LTC4, 5 microgram) to the LTC4 group (n = 8), the LTC4 antagonist, LY171883 (20 micrometer) to the LY171883 group (n = 8), and LTC4 (5 microgram) + ATP (10 micrometer) to the LTC4 + ATP group (n = 8) during normoxic ventilation. HPV responses were induced by three hypoxic challenges for 5 minutes separated by 5 minutes of ventilation with a normoxic gas mixture. Baseline pulmonary artery pressure change after exposure to each drug and hypoxic pressor response between a period 21% normoxic gas ventilation and that of 3% hypoxic gas ventilation were measured.
RESULTS
ATP and LTC4 + ATP increased baseline pulmonary artery pressures but LTC4 did not alter it. ATP did not affect hypoxic pressor response. Suramin, LY171883 and LTC4 + ATP inhibited the pressor response to hypoxia. LTC4 increased hypoxic pressor response.
CONCLUSIONS
In isolated rat lungs, HPV may be mediated by ATP and LTC4 appears more likely to be a modulator than a mediator of HPV.

Keyword

ATP; Hypoxic pulmonary vasoconstriction; Isolated rat lungs; Leukotriene C4; LY171883; Suramin

MeSH Terms

Acetophenones
Adenosine Triphosphate
Animals
Anoxia
Erythrocytes
Leukotriene C4
Leukotrienes
Lung
Muscle, Smooth
Oxygen
Pulmonary Artery
Pulmonary Circulation
Rats
Rats, Sprague-Dawley
Suramin
Tetrazoles
Vasoconstriction
Ventilation
Acetophenones
Adenosine Triphosphate
Leukotriene C4
Leukotrienes
Oxygen
Suramin
Tetrazoles