P rehypertension is highly prevalent worldwide.1 It is estimated that ≈30% to 50% of the population have this condition. It frequently complicates other cardiometabolic risk factors and is closely associated with coronary heart disease, stroke, and renal dysfunction.2 Early intervention in prehypertension substantially prevents the incidence of hypertension and related damage to target organs. Currently, several strategies are used to treat prehypertension, including the incorporation of therapeutic lifestyle changes, such as healthy dietary intake and regular physical activity, as well as the use of antihypertensive drugs, such as an angiotensin II receptor blocker. Although these treatments improve prehypertension, poor compliance and limitations associated with antihypertensive medications prevent their application in the general population. Thus, there is an urgent need to identify reliable and accurate measures to prevent the development of prehypertension.Taurine (2-aminoethanesulfonic acid) is the most abundant, semiessential, sulfur-containing amino acid. It can be synthesized in vivo by cysteine in the presence of cysteine dioxygenase, 3 but taurine is mainly acquired from dietary sources, such as eggs, meat, and seafood. Hydrogen sulfide (H 2 S) is synthesized from 2 sulfur-containing amino acids, l-cysteine and l-methionine, by the 3 enzymes, cystathionine-γ-lyase (CSE), cystathionine-β-synthetase (CBS), and 3-mercaptopyruvate sulfurtransferase. 4 Taurine has several potentially beneficial cardiovascular effects that involve regulation of the nitric oxide system and endothelial function, 5,6 the renin-angiotensin-aldosteroneAbstract-Taurine, the most abundant, semiessential, sulfur-containing amino acid, is well known to lower blood pressure (BP) in hypertensive animal models. However, no rigorous clinical trial has validated whether this beneficial effect of taurine occurs in human hypertension or prehypertension, a key stage in the development of hypertension. In this randomized, double-blind, placebo-controlled study, we assessed the effects of taurine intervention on BP and vascular function in prehypertension. We randomly assigned 120 eligible prehypertensive individuals to receive either taurine supplementation (1.6 g per day) or a placebo for 12 weeks. Taurine supplementation significantly decreased the clinic and 24-hour ambulatory BPs, especially in those with high-normal BP. Mean clinic systolic BP reduction for taurine/placebo was 7.2/2.6 mm Hg, and diastolic BP was 4.7/1.3 mm Hg. Mean ambulatory systolic BP reduction for taurine/placebo was 3.8/0.3 mm Hg, and diastolic BP was 3.5/0.6 mm Hg. In addition, taurine supplementation significantly improved endothelium-dependent and endothelium-independent vasodilation and increased plasma H 2 S and taurine concentrations. Furthermore, changes in BP were negatively correlated with both the plasma H 2 S and taurine levels in taurine-treated prehypertensive individuals. To further elucidate the hypotensive mechanism, experimental studies were perfor...

BackgroundMitochondrial Ca2+ homeostasis is fundamental to the regulation of mitochondrial reactive oxygen species (ROS) generation and adenosine triphosphate production. Recently, transient receptor potential channel, canonical type 3 (TRPC3), has been shown to localize to the mitochondria and to play a role in maintaining mitochondrial calcium homeostasis. Inhibition of TRPC3 attenuates vascular calcium influx in spontaneously hypertensive rats (SHRs). However, it remains elusive whether mitochondrial TRPC3 participates in hypertension by increasing mitochondrial calcium handling and ROS production.Methods and ResultsIn this study we demonstrated increased TRPC3 expression in purified mitochondria in the vasculature from SHRs, which facilitates enhanced mitochondrial calcium uptake and ROS generation compared with Wistar‐Kyoto rats. Furthermore, inhibition of TRPC3 by its specific inhibitor, Pyr3, significantly decreased the vascular mitochondrial ROS production and H2O2 synthesis and increased adenosine triphosphate content. Administration of telmisartan can improve these abnormalities. This beneficial effect was associated with improvement of the mitochondrial respiratory function through recovering the activity of pyruvate dehydrogenase in the vasculature of SHRs. In vivo, chronic administration of telmisartan suppressed TRPC3‐mediated excessive mitochondrial ROS generation and vasoconstriction in the vasculature of SHRs. More importantly, TRPC3 knockout mice exhibited significantly ameliorated hypertension through reduction of angiotensin II–induced mitochondrial ROS generation.ConclusionsTogether, we give experimental evidence for a potential mechanism by which enhanced TRPC3 activity at the cytoplasmic and mitochondrial levels contributes to redox signaling and calcium dysregulation in the vasculature from SHRs. Angiotensin II or telmisartan can regulate [Ca2+]mito, ROS production, and mitochondrial energy metabolism through targeting TRPC3.

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