Endotoxin interacts with tumor necrosis factor-alpha to induce vasodilation of isolated rat skeletal muscle arterioles.
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.
Glembot
T M
TM
Department of General Surgery, Eastern Virginia Medical School, Norfolk 23507, USA.
Britt
L D
LD
Hill
M A
MA
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
D004731:Endotoxins; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D009569:Nitric Oxide