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Abstract: In this study, the relationships between high water fluoride exposure and essential hypertension as well as plasma ET-1 levels were investigated. A total of 487 residents aged 40 to 75 were randomly recruited from eight villages in Zhaozhou County from Heilongjiang Province in China and were divided into 4 groups according to the concentrations of fluoride in their water. Consumption levels of drinking water fluoride for normal, mild, moderate, and high exposure groups were 0.84±0.26mg/L, 1.55±0.22mg/L, 2.49±0.30mg/L, and 4.06±1.15mg/L, respectively. The prevalence of hypertension in each group was 20.16%, 24.54%, 32.30%, and 49.23%, respectively. There were significant differences between all the groups; namely, with the increase in water fluoride concentrations, the risk of essential hypertension in adults grows in a concentration-dependent manner. Significant differences were observed in the plasma ET-1 levels between the different groups (P<0.0001). In the multivariable logistic regression model, high water fluoride concentrations (F− ≥3.01mg/L, OR4/1 =2.84), age (OR3/1 =2.63), and BMI (OR2/1 =2.40, OR3/1 =6.03) were closely associated with essential hypertension. In other words, the study not only confirmed the relationship between excess fluoride intake and essential hypertension in adults, but it also demonstrated that high levels of fluoride exposure in drinking water could increase plasma ET-1 levels in subjects living in fluoride endemic areas. [Copyright &y& Elsevier]