Cross talk of shear-induced production of prostacyclin and nitric oxide inendothelial cells

We tested the hypothesis that vessel homeostasis is maintained through the cross talk of shear-induced production of prostacyclin and nitric oxide (NO ). Confluent human umbilical vein endothelial cells (HUVEC) were exposed to fluid shear stress at 15 dyn/cm(2) using a cone-plate device, and the conc entrations of 6-keto-PGF(1 alpha), and NO metabolites (nitrate and nitrite) in the medium were measured with radioimmunoassay and the Greiss method, r espectively. Compared with static control, shear stress increased cumulativ e prostacyclin production by twofold after 90 min of exposure. Inhibition o f NO synthase enhanced flow-induced prostacyclin production by twofold with out affecting the baseline production. Guanylyl cyclase inhibitor enhanced flow-induced prostacyclin production to the same degree. In contrast, a sta ble agonist of cGMP attenuated the rapid early phase of flow-dependent pros tacyclin production. Shear-induced NO metabolite production was:unaffected even after indomethacin inhibited prostacyclin production. We conclude that NO shows an inhibitory effect on prostacyclin production under shear stres s and that vessel homeostasis may be maintained through an increase in pros tacyclin production when NO synthesis is impaired in endothelial cells.