DIFFERENTIAL EXPRESSION OF VASCULAR DYSFUNCTION OF SMALLER DIAMETER ARTERIES IN A RODENT MODEL OF METABOLIC SYNDROME

Abstract

Objective: Metabolic syndrome, driven by obesity and diabetes, is a major contributor to cardiovascular disease. While large arteries vascular dysfunction is a well-documented phenomenon of metabolic syndrome, vascular disease of smaller diameter arteries, which are key contributors to peripheral vascular resistance and blood pressure control, remains uncertain. Using in-vitro organ-bath preparation, this study, therefore, investigated functional responses of the superior mesenteric and right iliac arteries in a high fat diet (HFD)/streptozotocin-induced diabetes mellitus rat model. Design and method: Five-week-old male Wistar Albino rats (n = 24) were fed with either HFD (45 kcal% fat) or control diet (10 kcal% fat) for 10 weeks. At 10 weeks of age, 40 mg/kg streptozotocin and saline were injected intraperitoneally into the HFD and control groups, respectively. Results: Diabetic HFD rats displayed a time-dependent increase (p < 0.01) in water intake, urine output, fasting blood glucose and tailcuff systolic blood pressure compared to controls (154 ± 6 vs. 110 ± 4 mmHg). Both mesenteric and iliac vasoconstrictor responses (N/g) to norepinephrine (1E-9 – 3E-5 M), but not to the depolarizing signals of high potassium (5 – 120 mM), were greater (p < 0.01) in the HFD group relative to controls. Mesenteric, but not iliac, endothelium-dependent vasorelaxation to acetylcholine (1E-10 – 1E-5 M) was blunted (p < 0.05) in the HFD rats compared with controls. In contrast, mesenteric and iliac endothelium-independent vasorelaxation responses to sodium nitroprusside (1E-11 – 1E-6 M) remained comparable between groups. Conclusions: Vascular functional responses in smaller diameter arteries are differentially expressed in metabolic syndrome, demonstrating upregulated vasoconstriction to adrenergic stimuli and/or impaired endothelium-dependent relaxation. These vascular abnormalities align with those previously described in larger arteries and could therefore further promote the development of cardiovascular disease in metabolic syndrome.