Cyclooxygenase contracting factors and altered pulmonary vascular responses in chronically hypoxic newborn pigs. J Appl Physiol (1985) 2002 Jan;92(1):67-74
Date
12/18/2001Pubmed ID
11744644DOI
10.1152/jappl.2002.92.1.67Scopus ID
2-s2.0-0036092733 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
Pulmonary hypertension and blunted pulmonary vascular responses to ACh develop when newborn pigs are exposed to chronic hypoxia for 3 days. To determine whether a cyclooxygenase (COX)-dependent contracting factor, such as thromboxane, is involved with altered pulmonary vascular responses to ACh, newborn piglets were raised in 11% O(2) (hypoxic) or room air (control) for 3 days. Small pulmonary arteries (100-400 microm diameter) were cannulated and pressurized, and their responses to ACh were measured before and after either the COX inhibitor indomethacin; a thromboxane synthesis inhibitor, dazoxiben or feregrelate; or the thromboxane-PGH(2)-receptor antagonist SQ-29548. In control arteries, indomethacin reversed ACh responses from dilation to constriction. In contrast, hypoxic arteries constricted to ACh before indomethacin and dilated to ACh after indomethacin. Furthermore, ACh constriction in hypoxic arteries was nearly abolished by either dazoxiben, feregrelate, or SQ-29548. These findings suggest that thromboxane is the COX-dependent contracting factor that underlies the constrictor response to ACh that develops in small pulmonary arteries of piglets exposed to 3 days of hypoxia. The early development of thromboxane-mediated constriction may contribute to the pathogenesis of chronic hypoxia-induced pulmonary hypertension in newborns.
Author List
Fike CD, Pfister SL, Kaplowitz MR, Madden JAAuthor
Sandra L. Pfister PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AcetylcholineAnimals
Animals, Newborn
Calcimycin
Chronic Disease
Endothelium, Vascular
Female
Hypoxia
Male
Muscle Tonus
Muscle, Smooth, Vascular
Prostaglandin-Endoperoxide Synthases
Pulmonary Circulation
S-Nitroso-N-Acetylpenicillamine
Swine
Thromboxanes
