Abstract TH302: Biomechanical Analysis of Adiposity-Driven Hypertension: The Role of PVAT and Sex Differences in Dahl-SS Rats

Introduction: Hypertension and high adiposity are prevalent comorbidities, yet the biomechanics of adiposity-induced hypertension are not well-studied. Dahl-Salt Sensitive (Dahl SS) rats on a high-fat diet (HFD), which develop hypertension in both sexes, offer a model for studying this condition. We recently showed that including perivascular adipose tissue (PVAT) in the thoracic aortic wall reduces mechanical stress in normotensive rats, but its role in hypertension is unknown. Hypothesis: This study tested the hypothesis that the mechanics of central arteries (specifically the thoracic aorta, including PVAT) and peripheral arteries (third-order mesenteric arteries) are affected by HFD in an age-dependent manner. Additionally, since arterial mechanics differ by sex in other hypertension models, we explored whether HFD effects are modulated by sex. Methods: Female and male Dahl SS rats were fed either a control-fat diet (10% fat, CFD) or an HFD (60% fat) for 8 and 24 weeks after weaning. Mean arterial pressure (MAP) was measured (Fig. 1) and mechanical behaviors of arteries were tested under various loading conditions. Results and Conclusions: At 8 weeks, both sex (F>M on both diets) and diet (M on HFD > M on CFD) significantly affected aortic structural stiffness. PVAT lowered mechanical stress in the aortic wall, but this effect was decreased in females on a CFD compared to all other groups (Fig. 2 top). However, mesenteric arteries showed no significant changes (Fig. 3 top). The differences exhibited in the vasculature did not correlate with blood pressure differences. By 24 weeks, the structural stiffness of the thoracic aorta was equal across all groups. PVAT still maintained its beneficial effect, but this effect was significantly diminished in HFD females (Fig. 2 bottom). Significant remodeling was noted in mesenteric arteries, particularly reduced myogenic tone in females fed an HFD (Fig. 3 bottom). Unexpectedly, while HFD females had increased MAP, this was not linked to increased resistance via upregulated myogenic tone. Ultimately, sex and diet significantly influence vascular remodeling and blood pressure regulation in Dahl SS rats. Understanding these differences is crucial for developing targeted treatments for adiposity-driven hypertension.