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Inhibition of Matrix Metalloproteinase‐9 (MMP‐9) Reverses Changes in Vascular Wall Structure and Function of Thoracic Aorta of Dahl Salt‐Sensitive (DSS) Rats

Left ventricular hypertrophy and cardiac fibrosis in DSS‐hypertensive rats were associated with increased MMP‐9 and lowered TIMP‐4. The objective of this study was to determine if salt sensitive hypertension induced changes in vascular structure and function were ameliorated by inhibition of MMP‐9. Vascular function (isolated aortic rings) and levels of MMP‐9 and TIMP‐4 (Western blot, reverse zymography, and confocal staining) were determined in thoracic aorta segments of groups of 16 week male DSS, and Lewis control (L) rats on a normal salt or a high salt diet (8 wks). Rats were regrouped into DSS plus MMP‐9 inhibitor (SB‐3CT) treatment (D+I), and DSS without inhibitor (D). Acetylcholine‐induced relaxation responses were decreased in D as compared to L, but normalized in D+I. The contraction responses to phenylephrine increased by 20% in aortic rings from D as compared to L, but normalized in D+I. The sodium nitroprusside‐induced relaxation responses in all groups were not altered. The levels of MMP‐9 were higher in aortic segments from D as compared to the L, and were significantly reduced in D+I to levels comparable to those recorded for the L group. The levels of TIMP‐4 were lower in vessel segments from D as compared to L, but normalized in D+I. The results suggested that increase MMP‐9 instigated vascular hypertrophy and dysfunction in Dahl salt‐sensitive rats.