Effects of Tumor Necrosis Factor-α on Basal and Stimulated Endothelium-Dependent Vasomotion in Human Resistance Vessel

Abstract

The aim of this study was to determine whether tumor necrosis factor (TNF)-alpha would impair basal and stimulated endothelium-dependent vasomotion in human resistance vessel. Changes in baseline and acetylcholine (ACh)-induced forearm vascular resistance (FVR) were measured plethysmographically before and after a low-dose intraarterial forearm infusion of TNF-alpha according to the following three protocols in healthy volunteers. In the condition without pretreatment, basal FVR was significantly increased by TNF-alpha (from 30.5 +/- 4.8 to 39.9 +/- 5.9 units; p < 0.01), whereas ACh-induced minimal FVR did not differ between pre- and post-TNF-alpha states. In the condition after pretreatment with the cyclooxygenase inhibitor acetylsalicylic acid, although the vascular effects of TNF-alpha on basal FVR appeared to be blocked (37.1 +/- 5.3 vs. 37.6 +/- 5.2; NS), ACh-induced minimal FVR did not differ between pre- and post-TNF-alpha states. In the condition after pretreatment with the nitric oxide (NO) synthase inhibitor N(G)-monomethyl-L-arginine, the vascular effect of TNF-alpha on basal FVR was diminished, and the ACh-induced maximal dilatory response was significantly blunted after TNF-alpha compared with before TNF-alpha (minimal FVR: 30.4 +/- 12.0 vs. 12.3 +/- 4.2 units; p < 0.05). These findings suggest that brief exposure of the human forearm resistance artery to TNF-alpha may increase basal bioavailability of the vasoconstrictor prostaglandin and reduce basal bioavailability of NO. In the stimulated condition, TNF-alpha-induced vascular dysfunction may be overwhelmed by increased NO bioavailability in healthy humans.