Modification of vascular reactivity by alteration of intimal permeability: effect of TNF-alpha.
We investigated the effects of alterations in intimal permeability on microvascular reactivity to small hydrophilic agents in isolated, cannulated, perfused arterioles (65 +/- 6 microns ID) from hamster cheek pouches. Arterioles are 300-fold less responsive to the hydrophilic alpha 1-agonist, phenylephrine, applied to the lumen than when applied to the adventitia. Luminal treatment with tumor necrosis factor-alpha (TNF-alpha, 0.625 micrograms/ml, 1-2 h) potentiated reactivity to luminally applied phenylephrine, but the treatment did not change reactivity to adventitially applied phenylephrine. Similar results were obtained with a brief treatment with the detergent, 3-[(3-cholamidopropyl)dimethylammonio]-1- propanesulfonate (CHAPS; 0.3%, < 30 s). To confirm that a change in permeability had occurred, we measured the movement across the arteriolar wall of a low-molecular-weight hydrophilic fluorescent molecule, fluorescein, before and after luminal treatment with TNF-alpha or CHAPS. Either TNF-alpha or CHAPS significantly increased the rate of movement of fluorescein across the arteriolar wall. These data suggest that one element in the pathophysiology of TNF-alpha is an increase in arteriolar permeability to small, water-soluble agents, which may modify reactivity to circulating vasoactive substances.
Matsuki
T
T
Department of Physiology, University of Virginia School of Medicine, Charlottesville 22908.
Beach
J M
JM
Klindt
R L
RL
Duling
B R
BR
D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology*; D002793:Cholic Acids / Q000494:pharmacology; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D008854:Microscopy, Electron; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002793:Cholic Acids; D014409:Tumor Necrosis Factor-alpha; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate