High-salt and high-sucrose diets may not reliably induce hypertension or diabetes in rat models

Dietary models are commonly used in rodents to study hypertension and diabetes, but reported effects are inconsistent. We evaluated whether a 4 g% NaCl diet or a 65 kcal% sucrose diet reliably induces hypertension and hyperglycemia in Sprague–Dawley (SD) rats over 16 and 32 weeks. Thirty-five rats were assigned to baseline, 16-week, or 32-week cohorts, with weekly measurements of body mass index (BMI), mean arterial pressure (MAP), heart rate (HR), and non-fasting glucose levels. Fasting glucose levels were measured at study endpoints. Rats were categorized by blood pressure and glucose thresholds, and longitudinal, and cross-sectional analyses were performed. While over half of the high-salt rats were hypertensive at 16 weeks, no rats met criteria by 32 weeks (p < 0.001). Glucose classifications showed no significant differences across diets (p = 0.08). Longitudinal linear mixed-effects modeling revealed significant diet × time interactions (p < 0.0001), but trajectories were largely parallel, with BMI increasing modestly and MAP, HR, and glucose remaining stable. Overall, age and duration of exposure were the dominant drivers of cardiometabolic progression, with only transient or modest contributions from diet. These findings highlight the variability and context-dependence of diet-induced hypertension and diabetes models in SD rats and emphasize the need for supplemental approaches.