ENDOTOXIN INTERACTS WITH TUMOR NECROSIS FACTOR-α TO INDUCE VASODILATION OF ISOLATED RAT SKELETAL MUSCLE ARTERIOLES

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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-α (TNF-α) 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-α (.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 μg/mL Salmonella enteritidis ET for 1 h followed by a 2 min exposure to 100 ng/mL TNF-α demonstrated a dilation (to 128 ± 12%) that became statistically significant 10 min after TNF-α washout (to 142 ± 12%, p < .05). This effect was eliminated by combined inhibition of cycooxygenase (with indomethacin) and nitric oxide synthase (L-NAME). The data indicate that neither ET or TNF-α 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-α to cause arteriolar dilation, possibly through a mechanism involving both cyclooxygenase and nitric oxide synthase.

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