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Inflammatory agonists that increase microvascular permeability in vivo stimulate cultured pulmonary microvessel endothelial cell contraction

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Abstract

Bovine pulmonary microvessel endothelial cells grown on a flexible substrate contract upon the addition of angiotensin II, thrombin, bradykinin, and U44069, a stable analogue of thromboxane A2. All these agents promote inflammation and increase paracellular permeability in vivo or in vitro. The contractile response is mediated by intracellular and extracellular free calcium: the response is inhibited by TMB-8, an intracellular Ca2+ chelator, and EGTA. Contraction is inhibited by trifluoroperazine, a Ca2+-calmodulin antagonist, and by ML-7, an inhibitor of myosin light-chain kinase. Preincubation with PMA, a protein kinase C activator, prevents contraction by angiotensin II. The inactive analogue 4-α-phorbol 12,13-didecanoate does not inhibit contraction. In contrast cAMP, carbacyclin (a stable PGI2 analogue), and isoproterenol, agonists known to stabilize the microvascular barrier against inflammatory agents, relax pulmonary microvessel EC. This direct evidence of the contractile potential of microvessel endothelial cells lends support to the theory that endothelial contraction leads to increased junctional permeability.

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Authors and Affiliations

  1. Microvascular Research, Boston University, 5 Cummington Street, 02215, Boston, Massachusetts

    Nicole M. L. Morel & David Shepro

  2. Department of Surgery, School of Medicine, Cagliari, Sardinia

    Palmina P. Petruzzo

  3. Department of Surgery, Brigham and Women's Hospital Harvard Medical School, 02215, Boston, Massachusetts

    Herbert B. Hechtman

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  1. Nicole M. L. Morel
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  2. Palmina P. Petruzzo
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  3. Herbert B. Hechtman
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  4. David Shepro
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This work was supported in part by NIH Grants HL 16714, HL 33104, GM 24891, and GM 35141.

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Morel, N.M.L., Petruzzo, P.P., Hechtman, H.B. et al. Inflammatory agonists that increase microvascular permeability in vivo stimulate cultured pulmonary microvessel endothelial cell contraction. Inflammation 14, 571–583 (1990). https://doi.org/10.1007/BF00914277

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