title: Role of tumor necrosis factor-alpha in small intestinal microcirculation.
abstract: The systemic manifestations of sepsis are associated with increased cardiac output, peripheral vasodilatation, and mesenteric vasoconstriction. Our objective was to determine whether tumor necrosis factor (TNF)-alpha regulates small intestinal microcirculatory changes observed during sepsis. An intact loop of terminal ileum of an anesthetized rat was exteriorized into modified Krebs solution and then topically suffused with varying concentrations of TNF-alpha (10(-4) ng/ml to 10(2) ng/ml), norepinephrine (10(-4) M), and sodium nitroprusside (10(-5) M). Videomicroscopy was used to measure arteriolar (A1, A2, A3) and venular (V1, V2) diameter changes in response to topical TNF-alpha. First order vessel diameters did not change in response to TNF-alpha. However, second and third order arterioles dilated maximally by 35 +/- 16 and 52 +/- 12 per cent, respectively, in a dose dependent manner in response to TNF-alpha. Higher order vessels were more sensitive to TNF-alpha than lower order vessels. Norepinephrine (10(-4) M) produced vasoconstriction in all vessels tested (A2 18 +/- 3 per cent, p < 0.05; A3 6 +/- 6 per cent; V2 13 +/- 4 per cent, p < 0.05). Topical TNF-alpha caused dilation in preconstricted vessels as in the nonpreconstricted vessels. TNF-alpha induced vasodilation was prolonged and not reversed by removal of TNF-alpha. These data demonstrate statistically significant dilation in response to TNF-alpha in second and third order arterioles and venules of the small intestine. Persistent vasodilation suggests an induced mechanism of vasodilation in response to TNF-alpha that remains active even after removal of exogenous TNF-alpha. We, therefore, conclude that TNF-alpha causes persistent vasodilatation beyond the period of actual exposure to TNF-alpha in the small intestinal microcirculation. This effect is not altered by the presence of norepinephrine. These data suggest that small intestinal vasoconstriction observed during clinical conditions such as sepsis is unlikely to be mediated by TNF-alpha.
authors.affiliation: Department of Physiology, School of Medicine, University of Louisville, Kentucky, USA.
authors.forename: W
authors.initials: W
authors.lastname: Naziri
authors.forename: I G
authors.initials: IG
authors.lastname: Joshua
mesh_terms: D000818:Animals; D006439:Hemodynamics; D007082:Ileum / Q000098:blood supply / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012772:Shock, Septic / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha