Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin-angiotensin system and proinflammatory cytokines in hypertension

Toxicol Appl Pharmacol. 2014 Apr 15;276(2):115-20. doi: 10.1016/j.taap.2014.02.002. Epub 2014 Feb 25.

Abstract

Aims: To explore whether reactive oxygen species (ROS) scavenger (tempol) in the hypothalamic paraventricular nucleus (PVN) attenuates renin-angiotensin system (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and sympathetic activity in angiotensin II (ANG II)-induced hypertension.

Methods and results: Male Sprague-Dawley rats were infused intravenously with ANG II (10 ng/kg per min) or normal saline (NS) for 4 weeks. These rats were treated with bilateral PVN infusion of oxygen free radical scavenger tempol (TEMP, 20 μg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for 4 weeks. ANG II infusion resulted in increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These ANG II-infused rats also had higher levels of gp91(phox) (a subunit of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), and interleukin-1 beta (IL-1β) in the PVN than the control animals. Treatment with PVN infusion of TEMP attenuated the overexpression of gp91(phox), ACE and IL-1β within the PVN, and decreased sympathetic activity and MAP in ANG II-infused rats.

Conclusion: These findings suggest that ANG II infusion induces elevated PICs and oxidative stress in the PVN, which contribute to the sympathoexcitation in hypertension. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin-angiotensin system, proinflammatory cytokines and oxidative stress in ANG II-induced hypertension.

Keywords: Hypertension; Hypothalamic paraventricular nucleus; Oxidative stress; Proinflammatory cytokines; Renin–angiotensin system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology
  • Animals
  • Antioxidants / pharmacology*
  • Arterial Pressure / drug effects
  • Cyclic N-Oxides / pharmacology*
  • Hypertension / physiopathology*
  • Interleukin-1beta / analysis*
  • Male
  • Membrane Glycoproteins / analysis
  • NADPH Oxidase 2
  • NADPH Oxidases / analysis
  • Paraventricular Hypothalamic Nucleus / metabolism*
  • Peptidyl-Dipeptidase A / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism*
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology*
  • Spin Labels

Substances

  • Antioxidants
  • Cyclic N-Oxides
  • Interleukin-1beta
  • Membrane Glycoproteins
  • Reactive Oxygen Species
  • Spin Labels
  • Angiotensin II
  • Cybb protein, rat
  • NADPH Oxidase 2
  • NADPH Oxidases
  • Peptidyl-Dipeptidase A
  • tempol