Effects of indomethacin on newborn pig pial arteriolar responses to PCO2.
The present experiments were designed to determine whether hypocapnic cerebral vasoconstriction, like hypercapnic dilation, involves prostanoids and, if not, whether alternative mechanisms are related to the absolute arterial PCO2 (PaCO2) or the direction of change. We determined effects of indomethacin (5 mg/kg iv) on pial arteriolar responses to 1) increased PCO2 from normal, 2) decreased PCO2 from normal, and 3) increased PCO2 from hypocapnia to normocapnia in anesthetized newborn pigs. Pial arterioles constricted in response to hypocapnia (PaCO2 = 15-24 Torr) similarly before (-13 +/- 3%) and after (-16 +/- 2%) indomethacin. Cortical periarachnoid cerebrospinal fluid prostanoids were not increased by hypocapnia. As previously reported, cerebral vascular responses to hypercapnia (which increases cerebrospinal fluid prostanoids) were lost after indomethacin. To determine whether the failure of indomethacin to affect the responses to hypocapnia was due to the direction of change (decreasing) or the absolute level of PCO2, piglets were hyperventilated to approximately 15 Torr PaCO2. Increasing PaCO2 in these piglets to approximately 44 Torr caused pial arteriolar dilation (46 +/- 7%) that was not blocked by indomethacin (33 +/- 5%). Cortical periarachnoid prostanoids were not altered when PaCO2 was raised from hypocapnia to normocapnia. Therefore the relationship between CO2 and piglet cerebral vascular tone appears to involve multiple mechanisms. Specifically, dilation in response to CO2 above the normal range appears to involve prostanoids but changes in pial arteriolar diameter at low PaCO2 do not.
Mirro
R
R
Department of Pediatrics, University of Tennessee, Memphis 38163.
Pharris
L J
LJ
Armstead
W M
WM
Shibata
M
M
Leffler
C W
CW
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001158:Arteries; D001160:Arterioles / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood*; D006985:Hyperventilation / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010313:Partial Pressure; D010841:Pia Mater / Q000098:blood supply*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects
D002245:Carbon Dioxide; D009638:Norepinephrine; D007213:Indomethacin