• Ferrante S Gragasin and Sandra T Davidge.
• Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Canada. gragasin@ualberta.ca
• Am. J. Physiol. Heart Circ. Physiol. 2009 Jul 1;297(1):H466-74.

AbstractHypotension following administration of propofol, an anesthetic agent, is strongly predicted by advanced age and is partly due to direct vasodilation. We hypothesized that propofol increases nitric oxide (NO)-mediated vasodilation by enhancing its bioavailability in the aged adult vasculature, leading to greater vasodilation than in the young adult. Small mesenteric arteries from rats aged 13-15 versus 3 to 4 mo were compared in this study. Reactivity to propofol (1-100 microM) alone and with the addition of acetylcholine (ACh; 0.1-10 microM) in endothelial-intact and dunuded arteries following phenylephrine constriction was assessed using myography. N(G)-nitro-L-arginine methyl ester (L-NAME) and meclofenamate (Meclo) were used to inhibit NO and prostaglandin synthesis, respectively. Superoxide dismutase (SOD) and catalase were used as antioxidants during ACh relaxation and were compared with propofol in aging arteries. Propofol alone induced greater relaxation in 1) endothelial-intact compared with denuded arteries and 2) aged compared with young arteries, which were inhibited by L-NAME. ACh-induced relaxation was greater in young compared with aged control arteries; however, propofol pretreatment increased this relaxation in aged but not in young arteries. Additionally, propofol inhibited ACh-induced relaxation in arteries treated with L-NAME + Meclo [relaxation attributed to endothelium-derived hyperpolarizing factor (EDHF)]. Pretreatment with SOD and catalase increased relaxation to ACh in aged arteries similar to propofol. In conclusion, propofol causes relaxation in small mesenteric arteries in an endothelial-dependent and independent manner and increases ACh-induced relaxation in aged arteries. Interestingly, propofol inhibits EDHF-mediated relaxation but increases availability of NO, which leads to overall vascular relaxation.

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