The Restorative Effects of Eucommia ulmoides Oliver Leaf Extract on Vascular Function in Spontaneously Hypertensive Rats
Eucommia ulmoides Oliv. leaf is a traditional Chinese antihypertensive and antidiabetic medicine. We examined the effects of chronic Eucommia leaf extract (ELE) administration on artery function and morphology in spontaneously hypertensive rats (SHRs). ELE was orally administered via normal diet ad libitum to six-week-old male SHRs at a concentration of 5% for seven weeks. Acetylcholine (ACh)-induced endothelium-dependent relaxation, sodium nitroprusside (SNP)-induced endothelium-independent
... lium-independent relaxation, plasma nitric oxide (NO) levels, and media thickness were assessed. ELE significantly improved ACh-induced aortic endothelium-dependent relaxation but did not affect SNP-induced endothelium-independent relaxation in the SHRs, as compared to the animals receiving normal diet. Plasma NO levels and media thickness were significantly increased and decreased, respectively, in the ELE-treated SHRs. Therefore, long-term ELE administration may effectively improve vascular function by increasing plasma NO levels and bioavailability, and by preventing vascular hypertrophy in the SHR aorta. and antiproliferative endothelium-derived factors include nitric oxide (NO), endothelium-derived hyperpolarizing factor , and prostacyclin I 2  . NO is a particularly crucial factor in vascular homeostasis. Indeed, endothelial dysfunction is characterized by reduced NO production or activity and increased concentrations of endothelium-derived contracting factors  . Endothelial function may reflect an individual's lifestyle, as well as their propensity to develop atherosclerotic disease; the presence of endothelial dysfunction is considered to represent an important initial step in the development of atherosclerosis  . Eucommia ulmoides Oliver is the only known species of the genus Eucommia, which is the only genus in the Eucommiaceae family. The bark of E. ulmoides (Cortex Eucommiae) is used to produce herbal medicines that are traditionally used as analeptic, analgesic, sedative, antihypertensive, and diuretic drugs ; it is also used as a crude drug in Japan. Since the 1970s, Eucommia leaves (ELs) have been used in the Sichuan District of China as an antihypertensive drug and a health food  . In Japan, ELs are used in traditional beverages for health promotion. An EL product called "Tochu-cha" in Japanese is commercially available as a government-approved Food for Specified Health Uses for people with higher than normal blood pressure. Previously, several pharmacological studies reported that EL extract (ELE) also exhibited antihypertensive  , antihyperlipidemic , antioxidant , antihyperglycemic , insulin-sensitizing  , and anti-obesity effects [17, 18] . In particular, the antihypertensive effects of ELE were reported by in vivo and in vitro studies, indicating that ELE exhibited a dose-dependent blood-pressure-lowering effect in the spontaneously hypertensive rat (SHR)  and elicited an endothelium-dependent, NO-mediated vasorelaxation of the isolated rat aorta in vitro ; long-term intake also decreased blood pressure in human subjects with high normal blood pressure and mild hypertension [21, 22] . However, there is little information about the effects of long-term ELE intake on vascular function. Vessel endothelial dysfunction is a critical trigger of CVD and an independent predictor of cardiovascular events [23, 24] . Chronic endothelial dysfunction results in morphological changes of the arterial wall, such as hypertrophy, and initiation of atherosclerosis. Therefore, we examined the effects of chronic administration of ELE on SHR aortic endothelial function by examining acetylcholine (ACh)-induced relaxation and plasma NO levels, and on morphological changes by immunohistochemical analysis.