AimTo investigate the effect of non-specific matrix metalloproteinases (MMP) inhibitor, doxycycline(DOX), on hypertensive aortic remodeling.Methods80 male stroke-prone spontaneously hypertensive rats（SHR-SP） of 7 weeks age were randomly divided into 2 groups (DOX and control group, respectively, n=40 each).Five male Wistar-Kyoto rats (WKY) with same age were also investigated.SHR-SP were chronically treated from the end of 7 weeks after birth with doxycycline (30 mg/(kg·d)) in drinking water.Follow-up was terminated when the mortality rate of control group reached 50%.Rats were killed, and aorta was dissected and prepared for histological and biochemical assays.For pathological analysis, we used hematoxylin and eosin (HE) staining, Victoria blue (elastic fiber staining) and von Kossa silver (calcium staining). For biochemical analysis, soluble collagen assay and gelatin zymography were carried out.ResultsThere were no difference in intima perimeter, adventitia perimeter and media area in hypertensive rats. MMP-9 activity by gelatin zymography was not detected in all animals.Compared with control group, MMP-2 activity in dox group were significantly reduced ( 2.43±0.14 vs 3.15±0.23, P<0.05).Compared with control group, the ratio of elastic fiber area to intima area was dramatically decreased in DOX group ［(3.46%±1.62% vs 5.72%±3.87%, P<0.05)］. Sircol soluble collagen assay showed that there had no statistical difference between control and DOX groups (26.4±7.0 mg/g vs 28.0±8.7 mg/g, P>0.05).Although calcium deposition as revealed by von Kossa silver staining was no statistical difference between control and DOX groups, there was decreasing trend in DOX group (0.688%±0.718% vs 0.960%±0.999%, P=0.177).ConclusionDespite the fact that doxycycline could inhibit aortic MMP-2 activity in SHR-SP, in the setting of uncontrolled hypertension, doxycycline may aggravate the process of hypertensive aortic stiffening.