The effects of propofol on vascular function in mesenteric arteries of the aging rat

Abstract

Gragasin FS, Davidge ST. The effects of propofol on vascular function in mesenteric arteries of the aging rat. Hypotension 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 M) alone and with the addition of acetylcholine (ACh; 0.1-10 M) 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 ϩ 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. nitric oxide; endothelium-derived hyperpolarizing factor; oxidative stress LIFE EXPECTANCY HAS BEEN INCREASING steadily over the years in part due to advancements in medical care and technology. As a result, there is a greater proportion of the aging population seen perioperatively under the care of the anesthesiologist. Aging is associated with a multitude of physiological changes including alterations in the mechanics of the cardiovascular system such as arterial remodeling as well as impairment in endothelial function and an increase in oxidative stress (5). The anesthetic agent 2,6-diisopropylphenol (propofol) is widely used not only by anesthesiologists but also by emergency physicians, intensivists, and other acute care physicians. In the aging patient population, the use of propofol is a strong predictor of hypotension (28). This hypotension may be a result of myocardial depression (25), a decrease in sympathetic activity (29), and/or direct vascular relaxation (31).The precise mechanism of action of propofol on the vasculature is controversial and may involve direct modulati...

Pseudo-Leptomeningeal Contrast Enhancement at 3T in Pediatric Patients Sedated by Propofol

“…[3][4][5] Prior studies have also demonstrated that 2,6 diisopropyl phenol (propofol) can modulate CBF by decreasing the metabolic rate of oxygen; in addition, speculation based on animal studies suggests that propofol can dilate vascular smooth muscle in other regions of the body. 6 The basis of this study is that the authors had noted prominent LMCE on brain MR imaging in some sedated children, but based on clinical notes, they neither were acutely ill nor exhibited meningeal signs. Thus, this study was initiated to determine whether the degree of this phenomenon of apparent LMCE (termed here "pseudo"-LMCE) relates to the type of T1WI sequence, time to acquiring postcontrast T1WI, propofol dosage, or various patient demographics.…”

Vascular Aging and Hemodynamic Stability in the Intraoperative Period

“…In our studies, we demonstrated that propofol causes enhanced mesenteric artery relaxation in aged rats when compared to young, and this effect was attributed to increased NO bioavailability (Gragasin and Davidge, 2009). We also demonstrated that the combination of antioxidant enzymes superoxide dismutase and catalase enhance vasodilation to acetylcholine similar to propofol in aged rats (Gragasin and Davidge, 2009).…”

“…We also demonstrated that the combination of antioxidant enzymes superoxide dismutase and catalase enhance vasodilation to acetylcholine similar to propofol in aged rats (Gragasin and Davidge, 2009). On the basis of these studies, we suggested that propofol may exert part of its vasodilatory effects via intrinsic antioxidant effects (Ansley et al, 1998), since it is structurally similar to α-tocopherol (vitamin E).…”

Propofol increases the Ca2+ sensitivity of BKCa in the cerebral arterial smooth muscle cells of mice

“…However, there is a marked variability in cardiovascular sensitivity to propofol among patients. This variability may induce the serious side effect of hypotension, especially in elderly and hypertensive patients [5] . There are several mechanisms that are known to cause the hypotensive effects …”

“…However, propofol has the potential side effect of hypotension, which especially affects elderly patients [3] and hypertensive rats [4,5] . The wide variability of sensitivity to propofol may lead to circulatory instability among patients, the underlying mechanisms of which are complicated.…”