Inhibitory effect of indomethacin on prostacyclin receptor-mediated cerebral vascular responses.
The present study addresses the hypothesis that indomethacin, in addition to blocking prostaglandin synthesis, directly inhibits prostacyclin receptor-mediated cerebral vascular responses. To test this hypothesis, the effects of indomethacin on pial arteriolar dilation in response to the prostacyclin receptor agonist iloprost were investigated using a cranial window technique in newborn pigs. Topically applied iloprost resulted in dose-dependent pial arteriolar dilation and concomitant increases in cortical adenosine 3',5'-cyclic monophosphate (cAMP). Indomethacin (5 mg/kg iv + 10(-4) M topically) greatly reduced both the vasodilation and the increase in cortical cAMP in response to iloprost. In contrast, indomethacin did not attenuate beta-adrenoreceptor-mediated vasodilation and the increase in cortical cAMP in response to isoproterenol. Aspirin (50 mg/kg iv + 10(-3) M topically) did not affect pial arteriolar dilation or the increase in cortical cAMP in response to iloprost. Unlike indomethacin, aspirin was not effective in inhibiting prostanoid-associated cerebral vasodilation and increase in cortical cAMP in response to hypercapnia. The present data suggest that indomethacin selectively inhibits prostacyclin receptor-mediated responses in the newborn pig cerebral circulation. The combination of highly effective inhibition of prostaglandin H synthase and prostacyclin receptor-mediated vasodilation may contribute to the increased efficacy of indomethacin compared with other prostaglandin H synthase inhibitors in blocking certain vasodilator responses associated with prostanoids.
Parfenova
H
H
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163, USA.
Zuckerman
S
S
Leffler
C W
CW
D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006935:Hypercapnia / Q000503:physiopathology; D016285:Iloprost / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000502:physiology*; D013552:Swine
D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D016285:Iloprost; D007545:Isoproterenol; D001241:Aspirin; D007213:Indomethacin