Mineralocorticoids act centrally to regulate blood-borne tumor necrosis factor-α in normal rats

Joseph Francis; Terry Beltz; Alan Kim Johnson; Robert B Felder

doi:10.1152/ajpregu.00027.2003

Back

Mineralocorticoids act centrally to regulate blood-borne tumor necrosis factor-α in normal rats

Journal article

Peer reviewed

Mineralocorticoids act centrally to regulate blood-borne tumor necrosis factor-α in normal rats

Joseph Francis, Terry Beltz, Alan Kim Johnson and Robert B Felder

American journal of physiology. Regulatory, integrative and comparative physiology, Vol.285(6), pp.R1402-1409

12/2003

DOI: 10.1152/ajpregu.00027.2003

PMID: 14615404

View Online

Abstract

Excessive mineralocorticoid receptor (MR) stimulation induces neurohumoral excitation and cardiac and vascular fibrosis. In heart failure (HF) rats, with excessive neurohumoral drive, central infusion of the MR antagonist spironolactone (SL) decreases blood-borne TNF-alpha. This study aimed to determine whether DOCA, a precursor of aldosterone, acts centrally to stimulate TNF-alpha production in normal rats. DOCA (5 mg sc daily for 8 days) induced a progressive increase in TNF-alpha beginning on day 3 and increased tissue TNF-alpha in hypothalamus, pituitary, and heart but not in other brain and peripheral tissues harvested on day 9. A continuous intracerebroventricular infusion of SL (100 ng/h) blocked the plasma TNF-alpha response. Oral SL (1 mg/kg) blocked the plasma and tissue TNF-alpha responses. Thus DOCA increases TNF-alpha in brain, heart, and blood in normal rats. Activation of brain MR appears to account for the increase in plasma TNF-alpha. These findings have important implications for the understanding of pathophysiological states (e.g., HF, hypertension) characterized by high circulating levels of aldosterone.

Appetite

Tumor Necrosis Factor-alpha - metabolism

Pituitary Gland - metabolism

Sodium Chloride, Dietary - pharmacology

Receptors, Mineralocorticoid - metabolism

Injections, Intraventricular

Rats

Desoxycorticosterone - pharmacology

Male

Rats, Sprague-Dawley

Animals

Hypothalamus - metabolism

Spironolactone - pharmacology

Myocardium - metabolism

Mineralocorticoid Receptor Antagonists - pharmacology

Hypothalamus - drug effects

Pituitary Gland - drug effects

Details

Title: Subtitle: Mineralocorticoids act centrally to regulate blood-borne tumor necrosis factor-α in normal rats
Creators: Joseph Francis - Department of Internal Medicine,University of Iowa, Iowa City, Iowa 52242, USA
Terry Beltz
Alan Kim Johnson
Robert B Felder
Resource Type: Journal article
Publication Details: American journal of physiology. Regulatory, integrative and comparative physiology, Vol.285(6), pp.R1402-1409
Publisher: United States
DOI: 10.1152/ajpregu.00027.2003
PMID: 14615404
ISSN: 0363-6119
eISSN: 1522-1490
Grant note: HL-07121 / NHLBI NIH HHS R01-HL-63915 / NHLBI NIH HHS P01-HL-014388 / NHLBI NIH HHS
Language: English
Date published: 12/2003
Academic Unit: Psychological and Brain Sciences; Iowa Neuroscience Institute; Cardiovascular Medicine; Neuroscience and Pharmacology; Health and Human Physiology; Internal Medicine
Record Identifier: 9984065475802771

Metrics

13 Record Views

32 Times Cited - Web of Science