Differential regulation of the renin-angiotensin system by nicotine in WKY and SHR glia

J Mol Neurosci. 2008 Jun;35(2):151-60. doi: 10.1007/s12031-007-9025-7. Epub 2008 Mar 28.


Given that (1) the renin-angiotensin system (RAS) is compartmentalized within the central nervous system in neurons and glia (2) the major source of brain angiotensinogen is the glial cells, (3) the importance of RAS in the central control of blood pressure, and (4) nicotine increases the probability of development of hypertension associated to genetic predisposition; the objective of the present study was to evaluate the effects of nicotine on the RAS in cultured glial cells from the brainstem and hypothalamus of Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Ligand binding, real-time PCR and western blotting assays were used to compare the expression of angiotensinogen, angiotensin converting enzyme, angiotensin converting enzyme 2 and angiotensin II type1 receptors. We demonstrate, for the first time, that there are significant differences in the basal levels of RAS components between WKY and SHR rats in glia from 1-day-old rats. We also observed that nicotine is able to modulate the renin-angiotensin system in glial cells from the brainstem and hypothalamus and that the SHR responses were more pronounced than WKY ones. The present data suggest that nicotine effects on the RAS might collaborate to the development of neurogenic hypertension in SHR through modulation of glial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Angiotensinogen / genetics
  • Angiotensinogen / metabolism
  • Animals
  • Brain Stem / cytology
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Gene Expression / drug effects
  • Hypertension / metabolism
  • Hypertension / physiopathology*
  • Hypothalamus / cytology
  • Neuroglia / cytology
  • Neuroglia / drug effects*
  • Neuroglia / metabolism
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Renin-Angiotensin System / drug effects*
  • Renin-Angiotensin System / physiology


  • Nicotinic Agonists
  • RNA, Messenger
  • Receptor, Angiotensin, Type 1
  • Angiotensinogen
  • Nicotine
  • Peptidyl-Dipeptidase A
  • Ace2 protein, rat
  • Angiotensin-Converting Enzyme 2