ObjectiveBiosynthesis of eicosanoid metabolites in blood vessels regulates vascular tone and platelet function. We investigated whether intraluminal pressure modulates gene and protein expression of key eicosanoid enzymes in intact human conduit vessels and/or release of their vasoactive metabolites.MethodsPaired segments of human umbilical veins were perfused under laminar flow for 1.5, 3 and 6 h at high versus low intraluminal pressure (40/20 mmHg) with identical shear stress (10 dyn/cm2). Endothelial cell mRNAs encoding cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), prostaglandin synthase (PGS), and thromboxane synthase (TXS) were measured by quantitative real-time RT-PCR. Secretion of PGI2and TXA2to the perfusion medium was measured by enzyme immunoassay of their metabolites 6-keto-prostaglandin F1βand TXB2.ResultsIntraluminal pressures were 39.9±0.02 and 20.0±0.03 mmHg (P<0.0001) in high and low pressure circuits, and shear stress levels were 10.6±0.60 and 9.7±0.36 dyn/cm2(NS, not significant). COX-1 mRNA was significantly up-regulated after 1.5 h of high pressure stimulation and continued up to 3 h, but fell thereafter significantly below baseline after 6 h. COX-2 mRNA was initially significantly down-regulated, followed by a significant up-regulation after 6 h. Gene expressions of PGS and TXS were significantly induced after 6 h of high pressure perfusion. High pressure depressed the production of PGI2(P<0.05) but did not alter TXA2formation.ConclusionsIntraluminal pressure has differential effects on gene and protein expression of key eicosanoid enzymes and biosynthesis of prostanoid metabolites in intact human conduit vessles. The new, computerized biomechanical perfusion system may be a useful tool to elucidate specific effects of various biomechanical forces on intact mammalian conduit vessels.