Hypoxic pulmonary vasoconstriction in pigs: role of endothelin-1, prostanoids and ATP-dependent potassium channels.
This study investigated the mechanisms that may contribute to the hypoxic pulmonary vasoconstriction and compared the effects of hypoxia on pulmonary and systemic vascular beds. Six anesthetized spontaneously breathing pigs inhaled a hypoxic mixture (10% O2 in air) in control conditions and after pre-treatment with Indomethacin (3 mg kg(-1) i.v.) to block the cyclooxygenase pathway. During hypoxia, the Indomethacin pre-treated pigs were given Cromakalim (80 microg kg(-1) i.v.) to activate K+(ATP) channels. Bosentan (5 mg kg(-1) i.v.) was administered to block endothelin-1 receptors and then during hypoxia Cromakalim was administered as before. In all experimental conditions we recorded breathing pattern and vascular parameters: mean systemic and pulmonary arterial pressures; systemic and pulmonary vascular resistances; cardiac output; and heart rate. Vascular and respiratory responses to hypoxia were determined when PaO2 was reduced to 50 +/- 5 mmHg. The main finding was that in spontaneously breathing pigs, hypoxia induces pulmonary vasoconstriction and an increase in mean systemic arterial pressure, which are cyclooxygenase-independent. A role of endothelin-1 appears in both vascular districts, but pulmonary vasoconstriction may also be due to ET-1-dependent inhibition of K+(ATP) channels.
Istituto di Fisiologia Veterinaria e Biochimica, Università di Milano, Italy.
M
M
Albertini
M G
MG
Clement
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure; D000077300:Bosentan; D002302:Cardiac Output; D019806:Cromakalim / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D005260:Female; D006339:Heart Rate; D000860:Hypoxia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D015221:Potassium Channels / Q000502:physiology*; D011651:Pulmonary Artery / Q000503:physiopathology*; D012123:Pulmonary Ventilation; D013449:Sulfonamides / Q000494:pharmacology; D013552:Swine; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000502:physiology*
D000959:Antihypertensive Agents; D016861:Cyclooxygenase Inhibitors; D019332:Endothelin-1; D015221:Potassium Channels; D013449:Sulfonamides; D019806:Cromakalim; D000255:Adenosine Triphosphate; D000077300:Bosentan; D007213:Indomethacin