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

Abstract

Left ventricular hypertrophy (LVH) and cardiac fibrosis in DSS hypertensive rats were associated with matrix proteins alteration. DSS hypertension was characterized by a cardiac dysfunction. Present study determines if salt sensitive hypertension induced changes in vascular structure and function are attenuated by inhibition of MMP‐9. To test the hypothesis, vascular function and levels of MMP‐9 and TIM‐4 were determined in thoracic aorta segments of 16 week male DSS (D), and Lewis (L) rats. Groups were fed high salt diet for 6‐8 weeks. Rats were regrouped: DSS plus MMP‐9 inhibitor (SB‐3CT) treatment (D+I) and DSS without inhibitor (D). Aortic function was assessed on myobath. MMP‐9 and TIMP‐4 levels were measured by Western blot, reverse zymography and confocal staining. Acetylcholine‐induced relaxation response of the aortic rings was decreased in D as compared to L group, but normalized in D+I group. Sodium nitroprusside‐induced relaxation response was not altered. MMP‐9 levels were significantly high in aortic segments of D as compared to L group, and were significantly reduced in D+I group. There was significant decrease in TIMP‐4 levels in the D as compared to L group. The result suggests that increase in MMP‐9 instigates vascular hypertrophy and dysfunction in Dahl salt‐sensitive rats.