Asiatic acid attenuates renin-angiotensin system activation and improves vascular function in high-carbohydrate, high-fat diet fed rats.
BACKGROUND
In the rat model of high carbohydrate, high fat (HCHF) diet-induced metabolic syndrome (MS), previous studies have found that asiatic acid has an antihypertensive effect. In this study, we investigated effects of asiatic acid on vascular structure, vascular function and renin-angiotensin system (RAS) in HCHF diet-induced MS rats.


METHODS
Male Sprague-Dawley rats were divided into three treatment groups for the 15 week study: a control group fed a normal diet, a MS group fed HCHF diet plus 15 % fructose in their drinking water for 15 weeks, and an asiatic acid treated group that received a HCHF diet plus fructose for 15 weeks and also received orally administered asiatic acid (20 mg/kg BW/day) for the final 3 weeks. Vascular structure and function were investigated. AT1 receptor expression in aortic tissues and eNOS protein expression in the mesenteric arteries were detected. The levels of serum angiotensin (Ang) II, angiotensin converting enzyme (ACE) and plasma norepinephrine (NE) were measured. The differences among treatment groups were analyzed by one-way analysis of variance (ANOVA) followed by post-hoc Bonferroni tests.


RESULTS
At the end of the study, all rats fed a HCHF diet exhibited signs of MS including, hypertension, dyslipidemia and insulin resistance. Vascular remodeling in large and small arteries, overexpression of AT1 receptor, and high levels of serum Ang II and ACE were also observed in MS group (p < 0.05). Contractile responses to sympathetic nerve stimulation were enhanced relating to high plasma NE level in MS rats (p < 0.05). The response to exogenous NE was not changed in the mesenteric bed. Vasorelaxation responses to acetylcholine were blunted in thoracic aorta and mesenteric beds, which is consistent with downregulation of eNOS expression in MS rats (p < 0.05). Restoration of metabolic alterations, hemodynamic changes, RAS and sympathetic overactivity, increased plasma NE, endothelium dysfunction, and downregulation of eNOS expression was observed in the asiatic acid treated group (p < 0.05). However, asiatic acid failed to alleviate vascular remodeling in MS rats.


CONCLUSIONS
Our findings suggest that the observed antihypertensive effect of asiatic acid in MS rats might be related to its ability to alleviate RAS overactivity and improve vascular function with restoration of sympathetic overactivity.
Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
Putcharawipa
P
Maneesai
Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
Sarawoot
S
Bunbupha
Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
Upa
U
Kukongviriyapan
Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
Parichat
P
Prachaney
Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
Panot
P
Tangsucharit
Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
Veerapol
V
Kukongviriyapan
Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. ppoung@kku.ac.th.
Poungrat
P
Pakdeechote
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D059305:Diet, High-Fat; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy*; D053978:Pentacyclic Triterpenes / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D004040:Dietary Carbohydrates; D053978:Pentacyclic Triterpenes; C017032:asiatic acid
Asiatic acid; Metabolic syndrome; Rennin-angiotensin system; Vascular function