Journal article
Sex differences in the central and peripheral manifestations of ischemia-induced heart failure in rats
American journal of physiology. Heart and circulatory physiology, Vol.316(1), pp.H70-H79
01/01/2019
DOI: 10.1152/ajpheart.00499.2018
PMCID: PMC6383354
PMID: 30289294
Abstract
Sex differences in the presentation, outcome, and responses to treatment of systolic heart failure (HF) have been reported. In the present study, we examined the effect of sex on central neural mechanisms contributing to neurohumoral excitation and its peripheral manifestations in rats with HF. Male and female Sprague-Dawley rats underwent coronary artery ligation (CL) to induce HF. Age-matched rats served as controls. Ischemic zone and left ventricular function were similar 24 h and 4 wk after CL. Female rats with HF had a lower mortality rate and less hemodynamic compromise, pulmonary congestion, and right ventricular remodeling 4 wk after CL. Plasma angiotensin II (ANG II), arginine vasopressin (AVP), and norepinephrine levels were increased in HF rats in both sexes, but AVP and norepinephrine levels increased less in female rats. In the hypothalamic paraventricular nucleus, a key cardiovascular-related nucleus contributing to neurohumoral excitation in HF, mRNA levels for the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β as well as cyclooxygenase-2 and the ANG II type 1a receptor were increased in HF rats of both sexes, but less so in female rats. Angiotensin-converting enzyme 2 protein levels increased in female HF rats but decreased in male HF rats. mRNA levels of AVP were lower in female rats in both control and HF groups compared with the respective male groups. Activation of extracellular signal-regulated protein kinases 1 and 2 increased similarly in both sexes in HF. The results suggest that female HF rats have less central neural excitation and less associated hemodynamic compromise than male HF rats with the same degree of initial ischemic cardiac injury. NEW & NOTEWORTHY Sex differences in the presentation and responses to treatment of heart failure (HF) are widely recognized, but the underlying mechanisms are poorly understood. The present study describes sex differences in the central nervous system mechanisms that drive neurohumoral excitation in ischemia-induced HF. Female rats had a less intense central neurochemical response to HF and experienced less hemodynamic compromise. Sex hormones may contribute to these differences in the central and peripheral adaptations to HF.
Details
- Title: Subtitle
- Sex differences in the central and peripheral manifestations of ischemia-induced heart failure in rats
- Creators
- Yang Yu - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa , Iowa City, IowaShun-Guang Wei - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa , Iowa City, IowaRobert M Weiss - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa , Iowa City, IowaRobert B Felder - Research Service, Veterans Affairs Medical Center , Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.316(1), pp.H70-H79
- Publisher
- United States
- DOI
- 10.1152/ajpheart.00499.2018
- PMID
- 30289294
- PMCID
- PMC6383354
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Grant note
- R01 HL073986 / NHLBI NIH HHS R01 HL139521 / NHLBI NIH HHS R01 HL136149 / NHLBI NIH HHS
- Language
- English
- Date published
- 01/01/2019
- Academic Unit
- Iowa Neuroscience Institute; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984065383402771
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