Exposure to diisononyl phthalate induced an increase in blood pressure through activation of the ACE/ AT1R axis and inhibition of NO production.

摘要: Abstract Recent epidemiological studies have found that diisononyl phthalate (DINP) is associated with an increase in blood pressure. However, this correlation had not been clarified, nor has the underlying mechanism characterized. In study, C57/BL6 mice were exposed to DINP doses of 0.15 mg/kg/day, 1.5 mg/kg/day or 15 mg/kg/day for 6 weeks. Dexamethasone (DEXA) was used build hypertension model. After exposure and 1 mg/kg/day DEXA treatment, levels systolic pressure (SBP), diastolic (DBP), mean (MBP) heart rate (HR) determined, any histopathological changes targeted organs investigated. The results suggest treatment induced marked increases SBP, DBP, MBP, could also HR level. Along increase, pathological heart, aorta, kidney. To explore mechanism, we measured expression angiotensin converting enzyme (ACE), angiotensin-II type 1 receptor (AT1R) endothelial nitric oxide synthase (eNOS) as well (NO) concentration serum. data enhance ACE AT1R, inhibit eNOS NO production. Interestingly, 5 mg/kg/day inhibitor (ACEI) alleviated by treatment. These findings expand our understanding how impacts development hypertension, elucidates mechanisms.