Newborn piglet cerebral microvascular responses to epoxyeicosatrienoic acids

The present study on the newborn pig cerebral microcirculation determined the vasoactive properties of epoxyeicosatrienoic acids (EETs) and the contributions of prostaglandin cyclooxygenase to these properties. Pial arterioles of anesthetized piglets were observed through closed cranial windows, EETs were applied topically, and artificial cerebrospinal fluid from beneath the cranial windows was collected for the determination of adenosine 3',5'-cyclic monophosphate and 6-ketoprostaglandin F1 alpha. EETs caused dilation of pial arterioles and increased adenosine 3',5'-cyclic monophosphate. 5,6-EET produced a dose-dependent dilation at 10(-8) M and above, whereas 10(-6) M was required for 8,9-EET, 11,12-EET, and 14,15-EET. Indomethacin abolished pial arteriolar dilation to the EETs. However, EETs did not increase cortical 6-ketoprostaglandin F1 alpha concentration. Treatment of indomethacin-treated piglets with iloprost (10(-12) M topically) restored dilation to 5,6-EET. Neither isoproterenol nor sodium nitroprusside allowed vasodilation to 5,6-EET in indomethacin-treated piglets. Therefore, in the newborn pig cerebral microvasculature. EETs are potent vasodilators and prostacyclin-receptor agonists are necessary to allow this dilation to occur.