Cyclooxygenase-2 and an early stage of chronic hypoxia-induced pulmonary hypertension in newborn pigs.
Our objective was to determine whether cyclooxygenase (COX)-2-dependent metabolites contribute to the altered pulmonary vascular responses that manifest in piglets with chronic hypoxia-induced pulmonary hypertension. Piglets were raised in either room air (control) or hypoxia for 3 days. The effect of the COX-2 selective inhibitor NS-398 on responses to arachidonic acid or acetylcholine (ACh) was measured in endothelium-intact and denuded pulmonary arteries (100- to 400-microm diameter). Pulmonary arterial production of the stable metabolites of thromboxane and prostacyclin was assessed in the presence and absence of NS-398. Dilation to arachidonic acid was greater for intact control than for intact hypoxic arteries, was unchanged by NS-398 in intact arteries of either group, and was augmented by NS-398 in denuded hypoxic arteries. ACh responses, which were dilation in intact control arteries but constriction in intact and denuded hypoxic arteries, were diminished by NS-398 treatment of all arteries. NS-398 reduced prostacyclin production by control pulmonary arteries and reduced thromboxane production by hypoxic pulmonary arteries. COX-2-dependent contracting factors, such as thromboxane, contribute to aberrant pulmonary arterial responses in piglets exposed to 3 days of hypoxia.
Fike
Candice D
CD
Department of Pediatrics, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA. cfike@wfubmc.edu
Kaplowitz
Mark R
MR
Zhang
Yongmei
Y
Pfister
Sandra L
SL
D000818:Animals; D000831:Animals, Newborn; D016718:Arachidonic Acid / Q000378:metabolism*; D002908:Chronic Disease; D051546:Cyclooxygenase 2; D006976:Hypertension, Pulmonary / Q000201:enzymology* / Q000209:etiology; D000860:Hypoxia / Q000150:complications / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011651:Pulmonary Artery / Q000201:enzymology*; D015398:Signal Transduction; D013552:Swine; D014018:Tissue Distribution
D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases