Cerebral arteriolar dilation to hypoxia: role of prostanoids.
Experiments addressed the hypothesis that dilator prostanoids contribute to maintenance of low cerebral microvascular tone during hypoxia in the newborn. Anesthetized newborn pigs equipped with closed cranial windows were used to measure responses of pial arterioles (approximately 60 microns) to treatments. Hypoxia (Pao2 approximately equal to 25 mmHg) caused dilation of pial arterioles (approximately 50% increase in diameter). Hypoxia (5 min) caused an increase in cortical cerebrospinal fluid 6-ketoprostaglandin F1 alpha concentration from 907 +/- 171 (normoxia) to 1,408 +/- 213 pg/ml (hypoxia). Pretreatment with indomethacin (5 mg/kg) did not affect pial arteriolar dilation to hypoxia. Conversely, indomethacin treatment during hypoxia caused a rapid decrease in arteriolar diameter to nearly the normoxia diameter within 3 min, returning to the original hypoxia diameter by 10 min. Ibuprofen treatment (30 mg/kg) had no effect on pial arteriolar diameter during normoxia or hypoxia, and pretreatment did not alter dilation to hypoxia. However, pretreatment with ibuprofen abolished the constrictor effect of indomethacin given during hypoxia. These data suggest that the primary mechanism by which hypoxia produces cerebral vasodilation does not involve prostanoids, but prostanoids can contribute to cerebral vasodilation in response to hypoxia.
Leffler
C W
CW
Department of Physiology, University of Tennessee, Memphis 38163, USA.
Parfenova
H
H
D015121:6-Ketoprostaglandin F1 alpha / Q000134:cerebrospinal fluid; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D006935:Hypercapnia / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D011453:Prostaglandins / Q000502:physiology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D011453:Prostaglandins; D015121:6-Ketoprostaglandin F1 alpha; D007052:Ibuprofen; D007213:Indomethacin