Regulation of hypothalamic renin-angiotensin system and oxidative stress by aldosterone

Bing S. Huang, Hong Zheng, Junhui Tan, Kaushik P. Patel, Frans H.H. Leenen

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


In rats with salt-induced hypertension or postmyocardial infarction, angiotensin II type 1 receptor (AT1R) densities and oxidative stress increase and neuronal NO synthase (nNOS) levels decrease in the paraventricular nucleus (PVN). The present study was designed to determine whether these changes may depend on activation of the aldosterone -'ouabain' neuromodulatory pathway. After intracerebroventricular (i.c.v.) infusion of aldosterone (20 ng h-1) for 14 days, blood pressure (BP) and heart rate (HR) were recorded in conscious Wistar rats, and mRNA and protein for nNOS, endothelial NO synthase (eNOS), AT1R and NADPH oxidase subunits were assessed in brain tissue. Blood pressure and HR were significantly increased by aldosterone. Aldosterone significantly increased mRNA and protein of AT1R, P22phox, P47phox, P67phox and Nox2, and decreased nNOS but not eNOS mRNA and protein in the PVN, as well as increased the angiotensin-converting enzyme and AT1R binding densities in the PVN and supraoptic nucleus. The increases in BP and HR, as well as the changes in mRNA, proteins and angiotensin-converting enzyme and AT1R binding densities were all largely prevented by concomitant i.c.v. infusion of Digibind (to bind 'ouabain') or benzamil (to block presumed epithelial sodium channels). These data indicate that aldosterone, via 'ouabain', increases in the PVN angiotensin-converting enzyme, AT1R and oxidative stress, but decreases nNOS, and suggest that endogenous aldosterone may cause the similar pattern of changes observed in salt-sensitive hypertension and heart failure postmyocardial infarction.

Original languageEnglish (US)
Pages (from-to)1028-1038
Number of pages11
JournalExperimental Physiology
Issue number10
StatePublished - Oct 2011

ASJC Scopus subject areas

  • Physiology
  • Nutrition and Dietetics
  • Physiology (medical)


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