Tyrosine kinase inhibition attenuated both the shear-induced increase in L P and decrease in occludin content. Tyrosine kinase inhibition attenuated both.

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Tyrosine kinase inhibition attenuated both the shear-induced increase in L P and decrease in occludin content. Tyrosine kinase inhibition attenuated both the shear-induced increase in LP and decrease in occludin content. A: LP response to 20 dyn/cm2 with and without erbstatin A treatment (10 μM) is shown. At time 0, a hydrostatic pressure gradient of 10 cmH2O was applied and LP was measured for 1 h to establish a baseline. Addition of 20 dyn/cm2 at 60 min elicited a time-dependent increase inLP (n = 8 Transwell filters;n = 2 thoracic aortas). Compared with shear stress controls without the tyrosine kinase inhibitor, erbstatin A significantly inhibited the shear-LP response during the last hour of shear exposure (n = 4 Transwell filters; n = 1 thoracic aortas). *P < 0.05 vs. untreated sheared condition in A. B: immunoblot probed for occludin in BAECs unexposed to shear (lane C) and BAECs exposed to 20 dyn/cm2 for 3 h (lane 3h) with and without erbstatin A (Erb) treatment.C: Erb significantly attenuated the shear-induced decrease in occludin content (n = 6 glass slides;n = 1 thoracic aortas). There was no statistically significant difference in occludin content between control monolayers (lane C) and control monolayers treated with erbstatin A (lane C + Erb). D: BAEC monolayers were exposed to 10 dyn/cm2 for 4 h with and without 1 μM treatment of herbimycin A (Hrb), another tyrosine kinase inhibitor (blot not shown). Hrb also attenuated the shear-induced decrease in occludin content (n = 8 glass slides/n = 1 thoracic aortas). *P < 0.05 and **P < 0.005 vs. static control. Lucas DeMaio et al. Am J Physiol Heart Circ Physiol 2001;281:H105-H113 ©2001 by American Physiological Society