Effects of TNF-alpha on hemodynamic changes and circulating endothelium-derived vasoactive factors in dogs

Experimental analyses of whether tumor necrosis factor (TNF)-alpha affects hemodynamic modifications and endothelium-derived vasoactive factors in anesthetized dogs reveal that TNF-alpha enhances pulmonary and systemic vascular resistance and reduces MAP transiently. Endothelin (ET)-1 factor mediates the increases in vascular resistances due to TNF-alpha, while ET-3 and NO function as vasodilators for ET-1-induced vasoconstriction. Indomethacin or L-NNA pretreatment inhibits TNF-alpha-mediated hypotension and enhances systemic vascular resistance, indicating that TNF-alpha does not function through an NO-dependent pathway.