PS-B01-2: ASSOCIATION BETWEEN IMPAIRED METABOLIC FUNCTION AND VASCULAR DYSFUNCTION IN METABOLIC SYNDROME

Abstract

Objectives: Metabolic syndrome is a leading cause for vascular dysfunction and cardiovascular diseases. We have previously shown that vascular functional responses in metabolic syndrome exhibit exaggerated vasocontractility and impaired endothelium-dependent relaxation. However, it remains unclear if a correlation between vascular abnormalities and metabolic disturbances exists. Accordingly, we aimed to explore the association between vascular dysfunction and changes in metabolic parameters in a rodent model of metabolic syndrome, the high fat diet (HFD)-streptozotocin (STZ)-induced diabetes mellitus rat (HFD-D). Design and method: Five weeks old male Wistar albino rats (n = 24) were fed with either HFD (45 kcal% fat) or control diet (10 kcal% fat) for 10 weeks. On week 6, 40 mg/kg STZ and saline were injected intraperitoneally into the HFD and control groups, respectively. At the end of the treatment, metabolic data were collected then rats were euthanized for blood and kidney collection and to measure maximal vasoconstrictor and vasodilator responses of the abdominal aortic rings. Recorded measures also included fasting blood glucose (FBG), plasma total cholesterol (TC), plasma triglyceride (TG), plasma high density lipoprotein (HDL), plasma creatinine (Cr), urinary protein: urinary creatinine (UPC) and kidney index (KI). Results: HFD-D rats had higher FBG, TG, Cr, UPC, and KI compared with controls. HDL was lower in HFD-D while TC remained unchanged. Maximal vasoconstriction to norepinephrine (NE Rmax) was greater in the HFD group compared with controls. Maximal endothelium-dependent vasorelaxation to acetylcholine (ACh Rmax) was blunted in the HFD group relative to controls. A positive correlation between NE Rmax and FBG was found, whereas ACh Rmax was negatively correlated with FBG, KI, UPC and TG. Conclusions: Impaired glucose metabolism, lipid profile and renal function are likely key contributors to vascular dysfunction in metabolic syndrome; however, further mechanistic investigations are required to verify these assumptions.