Inflammatory agonists that increase microvascular permeability in vivo stimulate cultured pulmonary microvessel endothelial cell contraction.
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-alpha-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.
Morel
N M
NM
Boston University, Massachusetts 02215.
Petruzzo
P P
PP
Hechtman
H B
HB
Shepro
D
D
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000648:ultrastructure; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007365:Intercellular Junctions / Q000648:ultrastructure; D007545:Isoproterenol / Q000494:pharmacology; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011654:Pulmonary Edema / Q000503:physiopathology; D015290:Second Messenger Systems / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D000804:Angiotensin II; D014268:Trifluoperazine; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; C026678:carboprostacyclin; D004492:Edetic Acid; D011464:Epoprostenol; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase; D013917:Thrombin; D006152:Cyclic GMP; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate; D001920:Bradykinin; D002118:Calcium; D007213:Indomethacin