Chronic infusion of berberine into the hypothalamic paraventricular nucleus attenuates hypertension and sympathoexcitation via the ROS/Erk1/2/iNOS pathway

Phytomedicine. 2019 Jan:52:216-224. doi: 10.1016/j.phymed.2018.09.206. Epub 2018 Sep 22.

Abstract

Background: Berberine (BBR), a Chinese traditional herbal medicine, has many pharmacologic benefits such as anti-inflammation and anti-oxidation. It is widely used in clinical treatment of cardiovascular diseases such as hypertension. However, the mechanism of how BBR attenuates hypertension through affecting central neural system is not clear.

Purpose: This study was designed to determine whether chronic infusion of BBR into the hypothalamic paraventricular nucleus (PVN) attenuates hypertension and sympathoexcitation via the ROS/Erk1/2/iNOS pathway.

Methods: Two-kidney, one-clip (2K1C) renovascular hypertensive rats were randomly assigned and treated with bilateral PVN infusion of BBR (2μg/h) or vehicle (artificial cerebrospinal fluid) via osmotic minipumps for 28 days.

Results: 2K1C rats showed higher mean arterial pressure (MAP) and PVN Fra-like activity, plasma levels of norepinephrine (NE), PVN levels of NOX2, NOX4, Erk1/2 and iNOS, and lower PVN levels of copper/zinc superoxide dismutase (Cu/Zn-SOD). Chronic infusion of BBR reduced MAP, PVN Fra-like activity and plasma levels of NE, reduced NOX2, NOX4, Erk1/2, iNOS and induced Cu/Zn-SOD in the PVN.

Conclusions: These results suggest that BBR attenuates hypertension and sympathoexcitation via the ROS/Erk1/2/iNOS pathway in 2K1C renovascular hypertensive rats.

Keywords: Berberine; Erk1/2; Hypertension; Hypothalamic paraventricular nucleus; ROS; iNOS.

MeSH terms

  • Animals
  • Arterial Pressure
  • Berberine / pharmacology*
  • Hypertension / drug therapy*
  • MAP Kinase Signaling System*
  • Male
  • NADPH Oxidase 2 / metabolism
  • NADPH Oxidase 4 / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Norepinephrine / blood
  • Paraventricular Hypothalamic Nucleus / drug effects*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase-1 / metabolism

Substances

  • Reactive Oxygen Species
  • Berberine
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Superoxide Dismutase-1
  • Cybb protein, rat
  • NADPH Oxidase 2
  • NADPH Oxidase 4
  • Nox4 protein, rat
  • Norepinephrine