Mechanisms of Aortic Stiffness in Salt‐Sensitive Hypertension

Previously we have shown left ventricular hypertrophy and cardiac fibrosis in Dahl Salt‐Sensitive (DSS)‐hypertensive rats. We believe that arterial stiffness is also associated with DSS‐hypertension. To test the hypothesis that oxidative stress contributes to matrix remodeling of vascular wall by increasing MMP activity and impair vascular function in DSS hypertension, we looked at nitric oxide (NO) bioavailability, vascular function and levels of MMP‐9 and TIMP‐4 in thoracic aorta segments of 16 week male DSS, and Lewis (L) rats fed a high salt diet for 8 weeks. Groups were also treated with the antioxidant Tempol (T). Groups studied were: DSS; DSS+T; L and L+T. Acetylcholine‐induced relaxation responses were decreased by 40% in DSS as compared to L, but normalized in DSS+T group. The contraction response to phenylephrine decreased by 50% in aortic rings from DSS as compared to L group, but normalized in DSS+T group. The levels of MMP‐9 were higher and those of TMP‐4 lower in aortic segments from DSS as compared to the L, and they were normalized in DSS+T to levels comparable to those recorded for the L group. The results suggested that in DSS‐hypertensive rats, increase in oxidative stress is associated with both decreased NO availability and increased MMP‐9 expression which in turn contribute to vascular dysfunction and remodeling. Supported by grants from NIH‐NHLBI