title: Shear stress increases hydraulic conductivity of cultured endothelial monolayers.
abstract: To examine the effect of shear stress on hydraulic conductivity (Lp) of bovine aortic endothelial cell monolayers grown on polycarbonate filters, we developed a rotating disk system, which imposed a defined shear stress while Lp was measured. A 10-cmH2O pressure differential was applied to monolayers, and baseline Lp was established between 1.65 +/- 0.85 and 4.94 +/- 1.05 x 10(-7) cm.s-1.cmH2O-1. One-hour exposure to 10 dyn/cm2 shear stress caused a significant (P < 0.05) increase in Lp by 2.16-fold (+/- 0.42), and Lp remained elevated when shear stress was removed. Three-hour exposure to shear stresses between 0.1 and 20.0 dyn/cm2 revealed a threshold for shear-induced increase in Lp of 0.5 dyn/cm2. At 20 dyn/cm2, Lp initially decreased by 30% (+/- 13.4%, P < 0.05) and then increased to a level 3.76-fold (+/- 0.83, P < 0.05) greater than baseline Lp at 3 h. The shear-induced increase in Lp was reversed with dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP, 1 mM) and could be significantly (P < 0.05) inhibited when monolayers were preincubated with 0.3 mM DBcAMP, a concentration that did not significantly affect baseline Lp. Furthermore, preincubation with a general phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (1 mM), completely blocked the shear-induced increase in Lp. On the basis of these results, we conclude that shear stress alters endothelial Lp through a cellular mechanism involving signal transduction, not by a purely physical mechanism.
authors.affiliation: Department of Chemical Engineering, Pennsylvania State University, University Park 16802.
authors.forename: H W
authors.initials: HW
authors.lastname: Sill
authors.forename: Y S
authors.initials: YS
authors.lastname: Chang
authors.forename: J R
authors.initials: JR
authors.lastname: Artman
authors.forename: J A
authors.initials: JA
authors.lastname: Frangos
authors.forename: T M
authors.initials: TM
authors.lastname: Hollis
authors.forename: J M
authors.initials: JM
authors.lastname: Tarbell
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D010827:Physiology / Q000295:instrumentation; D013314:Stress, Mechanical; D013917:Thrombin / Q000494:pharmacology; D014867:Water / Q000378:metabolism*
chemical_list: D014867:Water; D003994:Bucladesine; D013917:Thrombin; D015056:1-Methyl-3-isobutylxanthine