**4.1 Molecular mechanisms of tea regulating blood pressure**

Evidence indicates that vascular superoxide anion inactivates nitric oxide (NO) and plays a critical role in the development of hypertension. NO reacts with superoxide anion to form peroxynitrite. Peroxynitrite can cause protein tyrosine nitration, which modifies protein structure and function and affects cell homeostasis, oxidizes LDL-C, and leads to reduced activity of endothelial nitric oxide synthase (eNOS) [44, 45]. Angiotensin II generates vascular superoxide anion by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Superoxide anion contributes to increased blood pressure, endothelial dysfunction, vascular remodeling, and sodium retention, consequently contributing to the development of hypertension (**Figure 2**). Possibly, green tea extract reduces the risk of hypertension by reducing vascular reactive oxygen species (ROS) formation and NADPH oxidase activity [37]. In rats, decaffeinated green tea extract stimulated the activation of the eNOS via the phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway [46].

Caveolin-1, the major negative regulator of eNOS activity, has its gene expression attenuated by green tea polyphenols via the activation of extracellular signal-regulated kinase 1/extracellular signal-regulated kinase 2 (ERK1/ERK2) and inhibition of p38 mitogen-activated protein kinase (MAPK) signaling pathways [47].

Another mechanism by which tea consumption can reduce the risk of hypertension is by inhibiting renin activity. The study conducted by Li et al. [48] showed that oolong and black tea extracts inhibited renin activity. The beneficial effect was attributed to thearubigins. However, monomeric catechins did not contribute to the inhibitory effect promoted by the tea extracts.

Endothelin-1 may contribute to hypertension by enhancing vascular superoxide anion production via ETA/NADPH oxidase. Evidence indicates that epigallocatechin gallate reduces endothelin-1 expression and secretion from endothelial cells, partly via Akt- and AMPK-stimulated forkhead box *transcription factor* class O1 (FOXO1) regulation of the endothelin-1 promoter [37].


*BMI, body mass index; EGCG, epigallocatechin gallate; HbA1C, glycated hemoglobin A1C; T2D, type 2 diabetes; ↓, reduction.*

#### **Table 2.**

*Clinical trials showing the tea effect on blood pressure.*

*Role of Tea Polyphenols in Metabolic Syndrome DOI: http://dx.doi.org/10.5772/intechopen.92888*

#### **Figure 2.**

*In hypertension, there is excessive ROS generation in endothelial cells induced by angiotensin II. ROS excess can stimulate the NF-kB pathway and increase endothelial inflammation. ROS excess may also increase LDL-C oxidation and inhibit prostacyclin; superoxide anion reacts with NO to form peroxynitrite, which is cytotoxic. The NO loss may reduce vasorelaxation and contribute to endothelial dysfunction and hypertension. Green tea extract may inhibit the ROS production as well as Oolong tea and black tea may inhibit renin, and consequently angiotensin II. Ang II: angiotensin II; AT1R: angiotensin II type 1 receptor; ICAM-1: intercellular adhesion molecule 1; LDL-ox: oxidized LDL-C; NF-kB: nuclear factor kappa B; NO: nitric oxide; ROS: reactive oxygen species; VCAM-1: vascular cell adhesion molecule 1. →: stimulation;* ⊥*: inhibition.*
