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 prostan oids and, if not, whether alternative mechanisms are related to the ab solute arterial P(CO2) (Pa(CO2)) or the direction of change. We determ ined effects of indomethacin (5 mg/kg iv) on pial arteriolar responses to 1) increased P(CO2) from normal, 2) decreased P(CO2) from normal, and 3) increased P(CO2) from hypocapnia to normocapnia in anesthetized newborn pigs. Pial arterioles constricted in response to hypocapnia ( Pa(CO2) = 15-24 Torr) similarly before (-13 +/- 3%) and after (-16 +/- 2%) indomethacin. Cortical periarachnoid cerebrospinal fluid prostano ids were not increased by hypocapnia. As previously reported, cerebral vascular responses to hypercapnia (which increases cerebrospinal flui d 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 P(CO2 ), piglets were hyperventilated to approximately 15 Torr Pa(CO2). Incr easing Pa(CO2) in these piglets to approximately 44 Torr caused pial a rteriolar dilation (46 +/- 7%) that was not blocked by indomethacin (3 3 +/- 5%). Cortical periarachnoid prostanoids were not altered when Pa (CO2) was raised from hypocapnia to normocapnia. Therefore the relatio nship 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 ar teriolar diameter at low Pa(CO2) do not.