Cardiovascular disease (CVD) is the number one cause of death in the U.S. and contributes to nearly one third of all global deaths. Current research has placed increasing emphasis on the fact that CVD is an inflammatory condition that is the result of a complex inflammatory response to an endothelial injury. Consequently, research is focused on investigating biomarkers of inflammation in an attempt to correlate them to risk of CVD.

Eicosanoids are the oxidative metabolites of arachidonic acid (AA), an ω-6 polyunsaturated fatty acid that is released in response to specific inflammatory stimuli. AA can be oxidized by one of three metabolic pathways to form prostaglandins, leukotrienes, or a number of hydroxyl and epoxy compounds. These eicosanoids have a variety of physiological functions including regulating inflammation.

A bioanalytical LC-ESI-MS method was developed and validated to separate and quantitate the major bioactive eicosanoids from all three metabolic pathways. The method is linear over several orders of magnitude and sensitive enough to quantitate endogenous levels of eicosanoids. Additionally, a solid phase extraction procedure was developed to isolate these compounds from biological rat matrices.

The method was applied to spontaneously hypertensive rats (SHR) to investigate the role of inflammation in the pathogenesis of CVD. Significant eicosanoid profile differences were observed between the SHRs and the normotensive Wistar Kyoto rats. Depressed renal PGE₂ production could represent renal dysfunction while elevated PGI₂ production in both the aorta and heart are responsible for vasodilation and are the result of a compensatory reaction to elevations in systemic blood pressure. ODecreased levels of cardiac PGE₂ may reflect the early beginnings of hypertrophy or fibrosis. Significantly elevated levels of thromboxane in the blood define the platelet activation that is known to occur in CVD. Decreased PGE ₂ levels in the blood also suggest that increased platelet function in these animals may predispose them to abnormal platelet aggregation and thrombotic events. Taken together, there appears to be considerable evidence that the eicosanoids can be used as biomarkers of the underlying inflammatory processes and may be useful in assessing cardiovascular risk by identifying pre-clinical abnormalities that will eventually become significant clinical CVD.