Journal article
Neurohumoral Regulation in Ischemia-Induced Heart Failure: Role of the Forebrain
Annals of the New York Academy of Sciences, Vol.940(1), pp.444-453
06/2001
DOI: 10.1111/j.1749-6632.2001.tb03697.x
PMID: 11458700
Abstract
Congestive heart failure (CHF) is characterized by neurohumoral excitation. Increased sympathetic drive and activation of the reninangiotensin-aldosterone system (RAAS), with vasoconstriction and volume retention, are hallmarks of the CHF syndrome. Treatment strategies have targeted the peripheral influences of these two systems, but have not addressed the central mechanisms that drive them. We monitored the development of CHF following coronary ligation in adult Sprague-Dawley rats. Left ventricular dysfunction characteristic of CHF was confirmed by echocardiography, and the CHF syndrome was validated by measurements of circulating hormones, sodium appetite, thirst, renal sodium and water retention, and renal sympathetic nerve activity (RSNA). In CHF rats, neuronal activity in the hypothalamic paraventricular nucleus (PVN), which mediates downstream effects of forebrain circumventricular organs, was increased and was inhibited by blocking components of the RAAS at the forebrain level. Forebrain (AV3V) lesions and intracarotid (forebrain directed) injections of agents (captopril, losartan, spironolactone) that block RAAS substantially attenuated the behavioral and physiological manifestations of CHF. Intravenous losartan and captopril, in doses that lower arterial pressure, increased RSNA. These findings demonstrate an important role for RAAS-activated forebrain mechanisms in CHF and suggest that the central neural mechanisms driving sympathetic nerve activity and volume retention may persist and promote the progression of CHF despite treatments directed toward the peripheral influences of RAAS.
Details
- Title: Subtitle
- Neurohumoral Regulation in Ischemia-Induced Heart Failure: Role of the Forebrain
- Creators
- ROBERT B FELDERJOSEPH FRANCISROBERT M WEISSZHI-HUA ZHANGSHUN-GUANG WEIALAN KIM JOHNSON
- Resource Type
- Journal article
- Publication Details
- Annals of the New York Academy of Sciences, Vol.940(1), pp.444-453
- DOI
- 10.1111/j.1749-6632.2001.tb03697.x
- PMID
- 11458700
- NLM abbreviation
- Ann N Y Acad Sci
- ISSN
- 0077-8923
- eISSN
- 1749-6632
- Publisher
- Blackwell Publishing Ltd
- Language
- English
- Date published
- 06/2001
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute; Cardiovascular Medicine; Neuroscience and Pharmacology; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984065479102771
Metrics
16 Record Views