This study addresses the role of nitric oxide (NO) and downstream signaling pathways in mediating the influences of oscillatory shear stress on the hydraulic conductivity (L-p) of bovine aortic endothelial cell (BAEC) monolayers. Exposure of BAEC monolayers to 20dyne/cm(2) steady shear stress for 3 h induced a 3.3-fold increase in L-p. When an oscillatory shear amplitude of 10dyne/cm(2) was superimposed on a steady shear of 10dyne/cm(2) to produce a non-reversing oscillatory shear pattern (10 +/- 10dyne/cm(2)), L-p increased by 3.0-fold within 90min. When the amplitude was increased to 15dyne/cm(2). resulting in a reversing oscillatory shear pattern (10 +/- 15dyne/cm(2)) the increase in L-p over 3h was completely Suppressed. Twenty and 10 +/-10dyne/cm(2) induced 2.9- and 2.6-fold increases in NO production above Don-sheared controls, respectively, whereas 10 +/- 15dyne/cm(2) stimulated a 14-fold increase in NO production. The inhibition of Lp with reversing oscillatory shear may be associated with alterations in cyclic guanosine monophosphate (cGMP) production downstream of NO which is up-regulated by reversing oscillatory shear, but is unaffected by steady shear. (C) 2002 Elsevier Science (USA). All rights reserved.