Functional study on vasodilator effects of prostaglandin E2 in the newborn pig cerebral circulation

Cerebral vascular reactivity to prostaglandin E2 was investigated in newborn pigs using closed cranial windows. Exogenous prostaglandin E2 is a dilator of pial arterioles that elevates cyclic AMP in cortical cerebrospinal fluid. Pial arterioles are less sensitive to prostaglandin E2 than to the prostacyclin receptor agonist iloprost, but their maximal responses to the dilator prostanoids are similar. The cerebrovascular effects of prostaglandin E2 and iloprost are not additive. Pretreatment with either iloprost or prostaglandin E2 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 E2 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 E2. These results suggest that vasodilator effects of prostaglandin E2 in the newborn cerebral circulation are mediated via prostacyclin receptors coupled to adenylyl cyclase.