Methyl Palmitate: A Potent Vasodilator Released in the Retina

Abstract

RRF and PAME share similar biochemical properties and react similarly to all pharmacologic inhibitors examined. Both act primarily on the voltage-dependent K+ (Kv) channel of aortic smooth muscle cells, causing aortic relaxation. These results suggest that PAME is the hydrophobic RRF.

Fatty acid methyl esters as a potential therapy against cerebral ischemia

“…Lin et al (2008) first reported that PAME released from SCG (the largest cervical ganglion in the sympathetic tract (Lee et al, 2011a(Lee et al, , 2011bLee et al, 2012;Wu et al, 2014)) is a novel vasodilator (Lin et al, 2008). Exogenous application of PAME directly onto the rabbit or rat thoracic aorta induced vasodilation in a concentration-dependent manner (Lin et al, 2008;Lee et al, 2010;Lee et al, 2011c). The EC 50 value (the concentration that induces 50% of the maximum relaxation) for PAME-elicited aortic vasodilation is 0.19 nM which is at least 178 times (vs. 34.8 nM) lower than that of sodium nitroprusside (NO donor)-induced vasodilation (BrizzolaraGourdie and Webb, 1997; Lin et al, 2008) indicating that PAME is a potent vasodilator.…”

“…However, it has also been shown that PAME spontaneously released from the retina is described as the retinaderived relaxing factor (Lee et al, 2010) which induces potent vasodilation in the pre-contracted rat aorta suggesting an important role in retinal circulation (Lee et al, 2010). In addition, PAME is also released from perivascular adipose tissue (PVAT), which has been reported to be PVAT-derived relaxing factor (Lee et al, 2011c) regulating systemic blood pressure.…”

“…The release of PAME from the SCG, PVAT, and retina, however, dramatically decreased in calcium-free Krebs' solution (Lee et al, 2010(Lee et al, , 2011cLin et al, 2008) indicating that calcium may be important for PAME release. Furthermore, the release of PAME from the SCG was reduced in the present of myosin light chain inhibition (Lin et al, 2008), which prevents synaptic vesicle pool mobilization (Ryan, 1999) suggesting that the release of PAME is possibly linked to synaptic vesicle exocytosis.…”

“…The exact mechanisms of PAME-induced vasodilation are not well-known. However, D108, page 3 of 6 Dossier R. Hui-Chao Lee et al: OCL 2016, 23(1) D108 PAME-induced aortic vasodilation is inhibited by voltagegated potassium (Kv) channel blockers such as tetraethylammonium and 4-aminopyridine in a concentration-dependent manner (Lee et al, 2010(Lee et al, , 2011c indicating that PAME may induce aortic vasodilation via opening Kv channels on vascular smooth muscle. The vasodilatory properties of PAME offer a potential therapeutic opportunity in the treatment against cerebral ischemia-induced hypoperfusion consequently promoting brain injury.…”

“…In addition, pre-treatment with PAME enhanced CBF and brain perfusion 24 h after asphyxial cardiac arrest-induced global ischemia to further attenuate neuronal cell death (Lin et al, 2014) indicating that PAME provides neuroprotection against cerebral ischemia via alleviating hypoperfusion following ischemia. SAME, a C18:0 saturated fatty acid, was co-released with PAME from SCG and the retina (Lee et al, 2010;Lin et al, 2008). Unlike PAME, exogenous administration of SAME was unable to induce aortic vasodilation (Lin et al, 2008).…”