This study compared two established dietary formulations, high salt and high fat-high carbohydrate, separately or in combination on the induction cardiovascular dysfunction. One-month-old C57BL/6J mice were fed one of the following diets for 3 mo: (1) control diet consisting of a high fat-high simple carbohydrate (HFHSC); (2) 8% NaCl diet (HS); or (3) HFHSC diet supplemented with 1% NaCl (HFHS). After 3 mo, the HFHSC mice demonstrated significantly increased end-diastolic volume and end-systolic volume, specifically increases of 35% and 78%, respectively (p<0.01) and a reduction of ventricular stiffness by 27% (p=0.015). The HS mice exhibited arterial hypertension with an increase of 33% in maximum end-systolic pressure (p=.024) and a decrease of 44% in arterial elastance (p=0.020), corroborated by an increase in the heart weight to body weight ratios (p=0.002) and vascular types I and III collagen (p=0.03 and p=0.0008, respectively). The HFHS group revealed a striking response of 230% to the α₁-adrenergic challenge (p=0.00034). These data suggest that the HFHSC diet causes dilaeed cardiomyopathy, whereas the HS diet produces arterial hypertension and the HFHS diet causes a vascular dysfunctional state that was highly responsive to α-adrenergic stimulation.