Rodent models of isolated systolic hypertension (ISH) are rare. One exception is the vitamin D and nicotine (VDN) model, in which arterial calcification raises arterial stiffness and vascular impedance. Complete analysis of the effect of VDN on ventricular-arterial interaction is lacking. Wistar rats were treated with VDN (VDN group, n = 9) and a control untreated group (CTRL, n = 10) was included. At sacrifice, invasive indexes of cardiac function were obtained using a conductance catheter. Aortic pressure and flow were measured to derive impedance and ventricular-arterial interaction. VDN caused significant increases in systolic (138±6 mmHg vs. 116±13 mmHg) and pulse pressure (42±10 mmHg vs. 26±4 mmHg). Arterial compliance decreased (0.12±0.08 ml/mmHg vs. 0.21±0.04 ml/mmHg CTRL) and pulse wave velocity increased significantly (8.8±2.5m/s vs. 5.1±2.0m/s CTRL). Elastic modulus rose in the VDN group. Preload recruitable stroke work and end-systolic elastance were both elevated in the VDN group thus decreasing the ratio of arterial elastance over end-systolic elastance (0.94±0.30 vs. 1.57±0.60 CTRL). Wave reflection was augmented in the VDN group, expressed by the increase in the wave reflection coefficient (0.63±0.06 vs. 0.52±0.05 CTRL), as well as the amplitude of the reflected pressure wave (13.3±3.1 mmHg vs. 8.4±1.0 mmHg CTRL). VDN lead to development of ISH and provoked alterations in cardiac function, arterial impedance, arterial function, and ventricular-arterial interaction, which in many aspects are similar to effects of an aged and stiffened arterial tree. The VDN model may be a useful model to study the patho-physiological effects of increased arterial stiffness.