Chronic administration of indomethacin increases role of nitric oxide in hypercapnic cerebrovasodilation in piglets.
Hypercapnia-induced cerebral vasodilation is associated with prostanoids in the piglet, but is a primarily nitric oxide (NO) associated response in many adult models. Hypercapnia-induced cerebral vasodilation is both NO and prostanoid associated in the juvenile pig. We hypothesized that with chronic administration of indomethacin the piglet would advance the role of the NO system in cerebrovascular responses. The closed cranial window technique was used in piglets to determine pial arteriolar response. Chronically indomethacin treated newborn animals dilated in response to CO2 similarly to control newborns (40.9+/-4.4% vs 48.4+/-4.1%). Topical n-nitro L-arginine (L-NA, 10(-3) M), attenuated CO2 induced dilation in the chronically indomethacin treated animals (11.7+/-3.3% vs 40.9+/-4.4%; p < 0.001), but had no effect on the response to hypercapnia of piglets not treated with indomethacin. Neither indomethacin nor L-NA altered response to topical isoproterenol (10(-6) M). We conclude that with chronic indomethacin administration there develops a significant hypercapnia-induced cerebral vasodilation in which NO has an important role. The chronic inhibition of the newborn's principal dilator system appears to increase the role of NO in newborn cerebral hemodynamics.
Son
Minnette
M
University of Texas Health Science Center, San Antonio, USA. Son@uthscsa.edu
Zuckerman
Samuel
S
D000287:Administration, Topical; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply* / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006935:Hypercapnia / Q000378:metabolism* / Q000503:physiopathology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine / Q000008:administration & dosage; D011897:Random Allocation; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D007213:Indomethacin