Background: Cardiovascular variability reflects autonomic regulation of blood pressure (BP) and heat rate (HR). However, systolic BP (SBP) variability also may be induced by fluctuations in stroke volume through left ventricular end diastolic pressure (LVEDP) variability via dynamic ventricular-arterial coupling during respiration. We hypothesized that dynamic ventricular-arterial coupling is modulated by changes in left ventricular compliance associated with altered preload and that a cascade control mechanism of ventricular-arterial coupling with arterial-cardiac baroreflex function contributes to the genesis of cardiovascular variability at the respiratory frequency. Methods and Results: Seven healthy young subjects underwent six minute recordings of beat-by-beat LVEDP, SBP and HR in the supine position with controlled respiration at 0.2 Hz during hyper- and hypovolemia. Spectral and transfer function analysis of these variables was conducted between 0.18-0.22 Hz. Dynamic ventricular-arterial coupling gain (Gain LVEDP-SBP) was smaller by 25% (P=0.009) during hypervolemia than hypovolemia while arterial-cardiac baroreflex function gain (Gain SBP-HR) was similar. As predicted from a cascade model, a linear relationship between Gain LVEDP-HR and LVEDP-SBP times Gain SBP-HR was identified (R²=0.93, P<0.001). Gain LVEDP-HR was smaller by 40% (P=0.04) during hypervolemia than hypovolemia, leading to a reduction in spectral power of HR variability by 45% (P=0.08). Conclusion: We conclude that dynamic ventricular-arterial coupling gain is reduced during hypervolemia due to a decrease in left ventricular compliance. A cascade model of ventricular-arterial coupling with the arterial-cardiac baroreflex contributes to the genesis of cardiovascular variability at the respiratory frequency.