The JNJ0966 Significantly Reduces the Elevated Serum MMP-9 and Blood Pressure Observed in SHRs With Periodontitis

INTRODUCTION AND AIMS: Periodontitis can cause increases in blood pressure and is a risk factor for poor control of hypertension. Previous studies have found that serum matrix metalloproteinase-9 (MMP-9) is significantly increased in patients with hypertension combined with periodontitis, but it has not been demonstrated whether elevated MMP-9 is related to elevated blood pressure. In this study, we examined whether serum MMP-9 and blood pressure are concomitantly elevated in spontaneously hypertensive rats (SHRs) with periodontitis and explored the potential mechanism. METHODS: Thirty-six 12-week-old male SHRs were randomly divided into an experimental periodontitis group (SHR-L, n = 18) and a nonperiodontitis group (SHR-C, n = 18). Four weeks later, the SHR-C and SHR-L groups were each randomly divided into 3 subgroups and received JNJ0966 (a specific inhibitor of MMP-9) by gavage once per day for 7 days at doses of 0, 10 and 30 mg/kg (n = 6 in each subgroup). Then, the noninvasive caudal artery pressure and serum concentrations of MMP-9, TIMP-1 and Ang II were measured. RESULTS: After 5 weeks of modelling, the MMP-9 levels and the MMP-9/TIMP-1 ratio, the Ang II concentration and the blood pressure measurement were all significantly higher in the SHR-L-0 group than in the SHR-C-0 group (P < 0.05). After intervention with JNJ0966, blood pressure and serum MMP-9 and Ang II levels were significantly lower in the SHR-C-30 group than in the SHR-C-0 group. Compared with those in the SHR-L-0 group, blood pressure, serum MMP-9 levels, the MMP-9/TIMP-1 ratio and Ang II levels were significantly lower in the SHR-L-10 and SHR-L-30 groups (P < 0.05). CONCLUSION: Systemic application of JNJ0966 can significantly reduce the elevated serum MMP-9 and blood pressure observed in SHR with periodontitis. CLINICAL RELEVANCE: This indicates that MMP-9 may be 1 mechanism underlying the increased blood pressure in patients with periodontitis.