title: Effects of tumor necrosis factor-alpha 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.
authors.affiliation: Second Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: N
authors.initials: N
authors.lastname: Arakawa
authors.forename: S
authors.initials: S
authors.lastname: Saitoh
authors.forename: M
authors.initials: M
authors.lastname: Satoh
authors.forename: K
authors.initials: K
authors.lastname: Hiramori
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine