Paraventricular Nucleus Infusion of Epigallocatechin-3-O-Gallate Improves Renovascular Hypertension

Cardiovasc Toxicol. 2016 Jul;16(3):276-85. doi: 10.1007/s12012-015-9335-x.

Abstract

Oxidative stress plays an important role in the pathogenesis of hypertension. Epigallocatechin-3-O-gallate (EGCG) is the main polyphenol present in green tea and is known for its potent antioxidant and anti-inflammatory properties. In the present study, we hypothesize that EGCG attenuates oxidative stress in the paraventricular nucleus of hypothalamus (PVN), thereby decreasing the blood pressure and sympathetic activity in renovascular hypertensive rats. After renovascular hypertension was induced in male Sprague-Dawley rats by the two-kidney one-clip (2K-1C) method, the rats received bilateral PVN infusion of EGCG (20 μg/h) or vehicle via osmotic minipump for 4 weeks. Our results were shown as follows: (1) Hypertension induced by 2K-1C was associated with the production of reactive oxygen species in the PVN; (2) chronic infusion of EGCG in the PVN decreased stress-related NAD(P)H oxidase subunit gp91(phox) and NOX-4 and increased the activity of antioxidant enzymes (SOD-1), also balanced the content of cytokines (IL-1β, IL-6, IL-10 and MCP-1) in the PVN, and attenuated the level of norepinephrine in plasma of 2K-1C rats. Our findings provide strong evidence that PVN infusion of EGCG inhibited renovascular hypertension progression through its potent anti-oxidative and anti-inflammatory activity in the PVN.

Keywords: Cytokines; Epigallocatechin-3-O-gallate; Hypertension; Hypothalamic paraventricular nucleus; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Antihypertensive Agents / administration & dosage*
  • Antioxidants / administration & dosage*
  • Blood Pressure / drug effects*
  • Catechin / administration & dosage
  • Catechin / analogs & derivatives*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Hypertension, Renovascular / drug therapy*
  • Hypertension, Renovascular / metabolism
  • Hypertension, Renovascular / physiopathology
  • Infusions, Parenteral
  • Male
  • Membrane Glycoproteins / metabolism
  • NADPH Oxidase 2
  • NADPH Oxidase 4
  • NADPH Oxidases / metabolism
  • Oxidative Stress / drug effects
  • Paraventricular Hypothalamic Nucleus / drug effects*
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Paraventricular Hypothalamic Nucleus / physiopathology
  • Rats, Sprague-Dawley
  • Superoxide Dismutase-1 / metabolism
  • Time Factors

Substances

  • Anti-Inflammatory Agents
  • Antihypertensive Agents
  • Antioxidants
  • Cytokines
  • Membrane Glycoproteins
  • Catechin
  • epigallocatechin gallate
  • Sod1 protein, rat
  • Superoxide Dismutase-1
  • Cybb protein, rat
  • NADPH Oxidase 2
  • NADPH Oxidase 4
  • NADPH Oxidases
  • Nox4 protein, rat