OPTIMIZATION OF EPOXYEICOSATRIENOIC ACID SYNTHESES TO TEST THEIR EFFECTS ON CEREBRAL BLOOD-FLOW IN-VIVO

Epoxyeicosatrienoic acids (EETs), normally present in brain and blood, appear to be released from atherosclerotic vessels in large amounts. Once intravascular, EETs can constrict renal arteries in vivo and dilate cerebral and coronary arteries in vitro. Whether EETs in blood will alter cerebral blood flow (CBF) in vivo is unknown. In the present study, the chemical synthesis of four EET regioisomers was optimized, and their identity and structural integrity established by chromatographic and mass spectral methods. The chemically labile EETs were converted to a sodium salt, complexed with albumin, and infused into anesthetized rats via the common carotid. The objective was to test whether sustained, high levels of intravascular EETs alter CBF. The CBF (cortical H-2 clearance) was measured before and 30 min after the continuous infusion of 14,15- (n = 5), 11,12- (n = 5), 8,9- (n = 7) and 5,6-EET (unesterified or as the methyl ester, n = 5 for each). Neither the CBF nor the systemic blood pressure was affected by EETs. Because the infusions elevated the plasma concentrations of EETs about 700-fold above normal levels (1.0 nM), it is unlikely that EETs released from atherosclerotic vessels will alter CBF.