Nitroglycerin reduces TNF-alpha toxicity to endothelial cells but compromises the protective effects of propofol

Abstract

Supplementation of nitroglycerin (NTG) may increase cardiomyocyte death during ischemia (Histol Histopathol 2009;24(12):1487–98) and the underlying mechanism is unknown. Vascular endothelial cell apoptosis precedes cardiomyocyte apoptosis during myocardial ischemia-reperfusion, a situation that is associated with increased tumor necrosis factor-α (TNF) production. We postulated that NTG may exacerbate TNF induced endothelial cell apoptosis by enhancing nitrative stress. Cultured human umbilical vein endothelial cells were either not treated (control), treated with TNF (40 ng/ml) alone or TNF in the presence of NTG, propofol (an anesthetic that scavenges peroxynitrite), or NTG plus propofol, respectively, for 16 hr. TNF increased endothelial cell apoptosis, accompanied by increased protein expression of nitrotyrosine, a footprint of peroxynitrite and an index of nitrative stress. Both NTG and propofol attenuated TNF-induced cell apoptosis, however this protective effect diminished when NTG and propofol were used in combination and this was accompanied by increased nitrotyrosine expression and protein kinase C-β2 phosphorylation at site ser660. NTG may have compromised propofol cellular protection by counteracting its peroxynitrite scavenging capacity.