A high-sodium diet induced significant aortic arterial stiffness (PWV 5.97 vs 2.39, p<0.001) at 6 weeks of age in stroke-prone Dahl salt-sensitive rats, preceding the onset of hypertension.
Does increased sodium intake induce arterial stiffness prior to hypertension in stroke-prone Dahl salt-sensitive rats?
Increased sodium intake induces arterial stiffness and epigenetic regulator gene expression changes prior to the onset of hypertension in salt-sensitive rats.
Absolute Event Rate: 5.97% vs 2.39%
p-value: p=<0.001
Multiple clinical studies show that arterial stiffness, measured as pulse wave velocity (PWV), precedes hypertension and is an independent predictor of hypertension end organ diseases including stroke, cardiovascular disease and chronic kidney disease. Risk factor studies for arterial stiffness implicate age, hypertension and sodium. However, causal mechanisms linking risk factor to arterial stiffness remain to be elucidated. Here, we studied the causal relationship of arterial stiffness and hypertension in the Na-induced, stroke-prone Dahl salt-sensitive (S) hypertensive rat model, and analyzed putative molecular mechanisms. Stroke-prone and non-stroke-prone male and female rats were studied at 3- and 6-weeks of age for arterial stiffness (PWV, strain), blood pressure, vessel wall histology, and gene expression changes. Studies showed that increased left carotid and aortic arterial stiffness preceded hypertension, pulse pressure widening, and structural wall changes at the 6-week time-point. Instead, differential gene induction was detected implicating molecular-functional changes in extracellular matrix (ECM) structural constituents, modifiers, cell adhesion, and matricellular proteins, as well as in endothelial function, apoptosis balance, and epigenetic regulators. Immunostaining testing histone modifiers Ep300, HDAC3, and PRMT5 levels confirmed carotid artery-upregulation in all three layers: endothelial, smooth muscle and adventitial cells. Our study recapitulates observations in humans that given salt-sensitivity, increased Na-intake induced arterial stiffness before hypertension, increased pulse pressure, and structural vessel wall changes. Differential gene expression changes associated with arterial stiffness suggest a molecular mechanism linking sodium to full-vessel wall response affecting gene-networks involved in vascular ECM structure-function, apoptosis balance, and epigenetic regulation.
Herrera et al. (Wed,) conducted a other in Salt-sensitive hypertension (n=22). High sodium diet vs. 0.23% NaCl diet was evaluated on Aortic pulse wave velocity (PWV) at 6 weeks of age (p=<0.001). A high-sodium diet induced significant aortic arterial stiffness (PWV 5.97 vs 2.39, p<0.001) at 6 weeks of age in stroke-prone Dahl salt-sensitive rats, preceding the onset of hypertension.