Abstract
Valsartan ameliorates hypothalamic indicators of inflammation and stress in Lewis and Fischer rats with ischemia‐induced heart failure
The FASEB journal, Vol.20(5), pp.A1203-A1203
03/2006
DOI: 10.1096/fasebj.20.5.A1203-c
Abstract
We hypothesized that “stress” contributes to upregulation of the brain renin‐angiotensin system (RAS) and the expression of inflammatory mediators in rats with ischemia‐induced heart failure (HF). Lewis (L) and Fischer 344 (F) rats underwent coronary ligation to induce HF (EF: F, 44.2±8.9%; L, 43.6±6.9%) or sham and were studied 6 weeks later. As expected, immunohistochemistry revealed that F but not L HF rats had increased (P<0.05, vs SHAM) corticotropin releasing hormone (CRH)‐positive neurons in hypothalamic paraventricular nucleus (PVN). Both F and L HF rats had more (P<0.05, vs SHAM) PVN neurons positive for Fra‐LI (indicator of chronic activation), angiotensin converting enzyme (ACE), cyclooxygenase (COX)‐2, nuclear factor kappa B (NF‐κB) p50 and interleukin (IL)‐1β, and more (P<0.05, vs SHAM) ACE, angiotensin type 1 receptor (AT1‐R), COX‐2 and NF‐κB p50 protein by Western blot in hypothalamus, more (P<0.05) in F than L. Treatment with AT1‐R blocker valsartan (VAL, 30 mg/kg/day orally) reduced (P<0.05) the increases in Fra‐LI‐, ACE‐, NF‐κB p50‐ and IL‐1β‐ positive PVN neurons, hypothalamic NF‐κB p50 protein, and plasma norepinephrine in F and L HF rats, more effectively (P<0.05) in L than F. Thus, L rats have impaired CRH, RAS and inflammatory responses to HF in hypothalamus and PVN. The results suggest one of two interpretations: either an increase in CRH is required for the full expression of brain RAS and the associated inflammatory responses, or L rats have an innately compromised brain RAS.
Details
- Title: Subtitle
- Valsartan ameliorates hypothalamic indicators of inflammation and stress in Lewis and Fischer rats with ischemia‐induced heart failure
- Creators
- Yu‐Ming Kang - University of IowaZhi‐Hua Zhang - University of IowaRalph F Johnson - University of IowaRobert M Weiss - University of IowaTerry G Beltz - University of IowaAlan Kim Johnson - University of IowaRobert B Felder - Veterans Affairs Medical Center
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.20(5), pp.A1203-A1203
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.20.5.A1203-c
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 03/2006
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute; Cardiovascular Medicine; Neuroscience and Pharmacology; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984071626602771
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