Functional study on vasodilator effects of prostaglandin E 2 in the newborn pig cerebral circulation

Abstract

Cerebral vascular reactivity to prostaglandin E 2 was investigated in newborn pigs using closed cranial windows. Exogenous prostaglandin E 2 is a dilator of pial arterioles that elevates cyclic AMP in cortical cerebrospinal fluid. Pial arterioles are less sensitive to prostaglandin E 2 than to the prostacyclin receptor agonist iloprost, but their maximal responses to the dilator prostanoids are similar. The cerebrovascular effects of prostaglandin E 2 and iloprost are not additive. Pretreatment with either iloprost or prostaglandin E 2 decreases pial arteriolar responsiveness to iloprost without affecting responses to isoproterenol. The homologous desensitization of pial arterioles suggests that auto- and cross-tachyphylaxis in vascular effects of iloprost and prostaglandin E 2 occur at the receptor level. Indomethacin, which selectively inhibits prostacyclin receptor-mediated responses in cerebral vascular smooth muscle, greatly reduces the vascular responses to prostaglandin E 2. These results suggest that vasodilator effects of prostaglandin E 2 in the newborn cerebral circulation are mediated via prostacyclin receptors coupled to adenylyl cyclase.