Hypertension is a well-documented predictive factor for cardiovascular events. Clinical studies have extensively demonstrated the differential hemodynamic consequences of various antihypertensive drugs, but failed to clearly elucidate the underlying mechanisms due to the difficulty in performing a quantitative deterministic analysis based on clinical data that carry confounding information stemming from interpatient differences and the nonlinearity of cardiovascular hemodynamics. In the present study, a multiscale model of the cardiovascular system was developed to quantitatively investigate the relationships between hemodynamic variables and cardiovascular properties under hypertensive conditions, aiming to establish a theoretical basis for assisting in the interpretation of clinical observations or optimization of therapy. Results demonstrated that heart period, central arterial stiffness, and arteriolar radius were the major determinant factors for blood pressures and flow pulsatility indices both in large arteries and in the microcirculation. These factors differed in the degree and the way in which they affect hemodynamic variables due to their differential effects on wave reflections in the vascular system. In particular, it was found that the hemodynamic effects of varying arteriolar radius were considerably influenced by the state of central arterial stiffness, and vice versa, which implied the potential of optimizing antihypertensive treatment by selecting proper drugs based on patient-specific cardiovascular conditions. When analyzed in relation to clinical observations, the simulated results provided mechanistic explanations for the beneficial pressure-lowering effects of vasodilators as compared to β-blockers, and highlighted the significance of monitoring and normalizing arterial stiffness in the treatment of hypertension.

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