LAUSR

Renovascular hypertension is characterized by activation of the renin-angiotensin-aldosterone system, blunted natriuretic responses, and elevated sympathetic nerve activity. Excess dietary salt intake exaggerates arterial blood pressure (ABP) in multiple models of experimental hypertension. The present study tested whether a high-salt diet exaggerated ABP and vascular dysfunction in a 2-kidney, 1-clip (2K1C) murine model. Male C57BL/6J mice (8–12 wk) were randomly assigned, and fed a 0.1% or 4.0% NaCl diet, and instrumented with telemetry units to measure ABP. Then, the 2K1C model was produced by placing a cuff around the right renal artery. Systolic, diastolic, and mean ABP were significantly higher in mice fed 4.0% vs. 0.1% NaCl at 1 wk but not after 3 wk. Interestingly, 2K1C hypertension progressively increased arterial pulse pressure in both groups; however, the magnitude was significantly greater in mice fed 4.0% vs. 0.1% NaCl at 3 wk. Moreover, pulse wave velocity was significantly greater in 2K1C mice fed 4.0% vs. 0.1% NaCl diet or sham-operated mice fed either diet. Histological assessment of aortas indicated no structural differences among groups. Finally, endothelium-dependent vasodilation was significantly and selectively attenuated in the aorta but not mesenteric arteries of 2K1C mice fed 4.0% NaCl vs. 0.1% NaCl or sham-operated control mice. The findings suggest that dietary salt loading transiently exaggerates 2K1C renovascular hypertension but promotes chronic aortic stiffness and selective aortic vascular dysfunction. NEW & NOTEWORTHY High dietary salt exaggerates hypertension in multiple experimental models. Here we demonstrate that a high-salt diet produces a greater increase in arterial blood pressure at 1 wk after induction of 2-kidney, 1-clip (2K1C) hypertension but not at 3 wk. Interestingly, 2K1C mice fed a high-salt diet displayed an exaggerated pulse pressure, elevated pulse wave velocity, and reduced endothelium-dependent vasodilation of the aorta but not mesenteric arteries. These findings suggest that dietary salt may interact with underlying cardiovascular disease to promote selective vascular dysfunction and aortic stiffness.