Hidden hemodynamic signatures in experimental hypertension: a translational framework for hypertensive vascular physiology
Y Alan, A Tas, N Tas, M I Bayhan, A Ozcan, J J Piek, K H Parker, M SezerAbstract
Background
Hypertension remains a major global health burden, yet the mechanisms driving the transition from physiological to hypertensive states are incompletely understood. Salt-induced hypertension is characterized by progressive arterial remodeling and complex pulsatile hemodynamics not fully captured by conventional blood pressure metrics. Using Dahl salt-sensitive (SS) and SS.13BN rat models, we applied reservoir–excess pressure analysis (REPA), which separates arterial pressure into reservoir (Pr) and excess (Pxs) components to characterize biomechanical alterations in arterial pressure during hypertensive progression.
Purpose
We used REPA in Dahl SS and SS.13BN rat models to characterize strain-dependent alterations in pressure waveform composition and reservoir–excess pressure balance during salt-induced hypertensive transition.
Methods
In this retrospective secondary analysis, high-fidelity arterial pressure waveforms from adult Dahl salt-sensitive (SS, n=9) and consomic SS.13BN (n=6) rats were analyzed. Paired radiotelemetry recordings were originally obtained at steady state under low-salt (LS, 0.4% NaCl) conditions and after 2 weeks of high-salt (HS, 8.0% NaCl) diet. REPA was performed to decompose waveforms into reservoir (Pr) and excess (Pxs) components. Pressure-only wave intensity analysis (WIA) was used to quantify forward (FCW) and backward (BCW) compression waves and to calculate the wave reflection index (WRI = BCW/FCW), thereby assessing arterial wave energy transfer and distal impedance mismatch across dietary conditions.
Results
The high-salt (HS) diet significantly increased arterial pressures and REPA parameters in both strains, except for Pxs in consomic SS.13BN rats. Linear mixed-effects models demonstrated a significant strain × diet interaction for Pxs, with significant effects of diet (β = −1.445, 95% CI −1.913 to −0.977; p < 0.001) and strain (β = −1.699, 95% CI −2.481 to −0.918; p < 0.001), as well as a significant interaction term (β = 1.055, 95% CI 0.118 to 1.992; p = 0.037), demonstrating a more pronounced salt-induced increase in Pxs in Dahl SS rats compared with SS.13BN rats. Consistent with this, SS.13BN rats did not show a statistically significant change in Pxs between LS and HS conditions (3.94 [3.47–4.94] vs 5.24 [4.83–5.56]; p = 0.099) and exhibited higher IntPr/IntPxs ratios than Dahl SS rats when analyzed across both dietary conditions (p = 0.020), indicating a greater relative contribution of reservoir pressure to the pressure waveform in SS.13BN rats.
Conclusions
This animal-model analysis using REPA demonstrates strain-specific blood pressure responses to dietary salt. Reservoir pressure, reflecting arterial reservoir function, may capture genetically determined differences in hemodynamic adaptation to salt-induced hypertensive stress. These findings may inform targeted therapeutic strategies addressing the pathophysiological heterogeneity of hypertension.Fig 1 Arrows show LS-to-HS mean % change (SD)For image description, please refer to the figure legend and surrounding text.Table 1For image description, please refer to the figure legend and surrounding text.