Biomechanical adaptation of the thoracic aorta and its perivascular adipose tissue precedes hypertension development in Dahl Salt-Sensitive rats on high-fat diet

This study aimed to quantify sex-dependent biomechanical adaptation mechanisms occurring at or just before significant blood pressure increases in high-fat diet (HFD)-fed Dahl Salt Sensitive (Dahl-SS) rats. The early adaptation stages were analyzed to provide insights for hypertension prevention. Female and male rats were fed a control-fat diet (10% fat-CFD) or an HFD (60% fat) for 16-17 weeks from weaning, and their thoracic aorta (with and without perivascular adipose tissue, +/-PVAT) was analyzed. Biomechanical properties such as pulse wave velocity (PWV), stiffness at in vivo stress, structural stiffness, and tissue composition were measured. In females, early adaptive remodeling occurred primarily in the thoracic aortic wall (-PVAT), including increased structural and material stiffness, elevated PWV, and medial changes with increased smooth muscle cell content and reduced collagen, which preceded the substantial blood pressure rise. Conversely, males showed early signs of maladaptive responses in the PVAT and adventitial layers, characterized by structural stiffening, decreased elastic stored energy at in vivo stress, and increased collagen area fraction, indicative of fibrosis and impaired vascular function. At baseline (CFD-fed), males demonstrated larger lumen diameters and structurally stiffer stress-stretch behavior compared to females. These findings highlight distinct sex-dependent remodeling pathways in response to HFD: females exhibited compensatory adaptive remodeling, while males showed signs of maladaptive responses, both occurring before significant blood pressure increases. STATEMENT OF SIGNIFICANCE: This study examines sex-dependent biomechanical changes in high-fat diet-fed Dahl Salt Sensitive rats before significant blood pressure increases. By focusing on the early stages of thoracic aorta adaptation, the research seeks to provide insights into hypertension prevention. The findings indicate that female rats experience beneficial early remodeling, evidenced by increased arterial wall stiffness and changes in smooth muscle cells and collagen. In contrast, male rats exhibit detrimental responses, such as stiffening of adipose tissue and reduced elastic energy. These sex-specific differences in response to high-fat diets highlight potential strategies for targeted hypertension prevention and contribute valuable data to cardiovascular health research.