Prostaglandins and Defects in Vascular Function

Abstract

Atherosclerotic arterial lesions have been reported to exhibit altered arachidonic acid metabolism (1–4). These alterations have consistently involved decreases in arterial prostacyclin (prostaglandin I₂ or PGI₂) synthesis; arterial thromboxane A₂ (TXA₂) formation (3) and increased PGE₂ formation (2) have also been associated with atherosclerotic lesions. Conversely, it has been recently reported that total urinary excretion of 2,3-dinor-6-keto-PGFl_α, one of the metabolites of PGI₂ produced. in vivo, is higher in patients with severe atherosclerosis than normal subjects (5). It was suggested that there was an increase in PGI₂ formation due to stimulation of PGI₂ synthetase as there may be increased platelet-endothelial interactions in patients with severe atherosclerosis. The present study reports that there are graduated decreases in human arterial PGI₂ synthetase activity within atherosclerotic plaque but that these decreases are focal, as the arterial regions immediately adjacent to the plaque exhibit normal PGI₂ synthetase activity.