title: Endotoxin interacts with tumor necrosis factor-alpha to induce vasodilation of isolated rat skeletal muscle arterioles.
abstract: Sepsis is characterized by decreased peripheral vascular resistance, however, discrepancies exist regarding the specific secondary mediators involved. This study examined whether the presence of endotoxin (ET) is a requirement for tumor necrosis factor-alpha (TNF-alpha) to induce vasodilation of isolated skeletal muscle arterioles. First order cremasteric arterioles were isolated from male Sprague-Dawley rats, cannulated with glass micropipettes, superfused in physiologic saline, and allowed to achieve spontaneous basal tone in the absence of intraluminal flow. A 2 min exposure to TNF-alpha (.01-100 ng/mL) had no apparent effect on arteriolar diameter (95 +/- 5% after .01 ng/mL and 92 +/- 6% after 100 ng/mL, p > .05 compared with basal). However, arterioles superfused with 2.5 micrograms/mL Salmonella enteritidis ET for 1 h followed by a 2 min exposure to 100 ng/mL TNF-alpha demonstrated a dilation (to 128 +/- 12%) that became statistically significant 10 min after TNF-alpha washout (to 142 +/- 12%, p < .05). This effect was eliminated by combined inhibition of cycloxygenase (with indomethacin) and nitric oxide synthase (L-NAME). The data indicate that neither ET or TNF-alpha alone elicit a direct vasomotor effect on the isolated arteriole preparation used in these studies. However, pretreatment of the vessels with ET results in the ability of TNF-alpha to cause arteriolar dilation, possibly through a mechanism involving both cyclooxygenase and nitric oxide synthase.
authors.affiliation: Department of General Surgery, Eastern Virginia Medical School, Norfolk 23507, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Glembot
authors.forename: L D
authors.initials: LD
authors.lastname: Britt
authors.forename: M A
authors.initials: MA
authors.lastname: Hill
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000648:ultrastructure; D004731:Endotoxins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004731:Endotoxins; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D009569:Nitric Oxide