Inhibitory effect of indomethacin on prostacyclin receptor-mediated cerebral vascular responses

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Abstract

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 β- 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume268
Issue number5 37-5
StatePublished - Jan 1 1995

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Epoprostenol Receptors
Indomethacin
Blood Vessels
Iloprost
Cyclic AMP
Vasodilation
Prostaglandins
Dilatation
Prostaglandin-Endoperoxide Synthases
Aspirin
Cerebrovascular Circulation
Swine
Cyclooxygenase Inhibitors
Hypercapnia
Vasodilator Agents
Isoproterenol

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

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title = "Inhibitory effect of indomethacin on prostacyclin receptor-mediated cerebral vascular responses",
abstract = "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 β- 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.",
author = "Elena Parfenova and S. Zuckerman and Charles Leffler",
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AU - Parfenova, Elena

AU - Zuckerman, S.

AU - Leffler, Charles

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N2 - 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 β- 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.

AB - 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 β- 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.

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