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Paraventricular nucleus corticotrophin releasing hormone contributes to sympathoexcitation via interaction with neurotransmitters in heart failure

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Abstract

Recent studies indicate that systemic administration of tumor necrosis factor (TNF)-α induces increases in corticotrophin releasing hormone (CRH) and CRH type 1 receptors in the hypothalamic paraventricular nucleus (PVN). In this study, we explored the hypothesis that CRH in the PVN contributes to sympathoexcitation via interaction with neurotransmitters in heart failure (HF). Sprague–Dawley rats with HF or sham-operated controls (SHAM) were treated for 4 weeks with a continuous bilateral PVN infusion of the selective CRH-R1 antagonist NBI-27914 or vehicle. Rats with HF had higher levels of glutamate, norepinephrine (NE) and tyrosine hydroxylase (TH), and lower levels of gamma-aminobutyric acid (GABA) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN when compared to SHAM rats. Plasma levels of cytokines, NE, ACTH and renal sympathetic nerve activity (RSNA) were increased in HF rats. Bilateral PVN infusions of NBI-27914 attenuated the decreases in PVN GABA and GAD67, and the increases in RSNA, ACTH and PVN glutamate, NE and TH observed in HF rats. These findings suggest that CRH in the PVN modulates neurotransmitters and contributes to sympathoexcitation in rats with ischemia-induced HF.

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Abbreviations

AP:

Arterial pressure

ANOVA:

Analysis of variance

BW:

Body weight

CRH:

Corticotrophin releasing hormone

dpPVN:

Dorsal parvocellular PVN

ECD:

Electrochemical detection

EPI:

Epinephrine

ELISA:

Enzyme-linked immunosorbentassay

GABA:

Gamma-aminobutyric acid

GAD67:

67-kDa isoform of glutamate decarboxylase

GLU:

Glutamate

HF:

Heart failure

HPA:

Hypothalamo–pituitary–adrenal axis

HPLC:

High performance liquid chromatography

HR:

Heart rate

IZ:

Ischemic zone

IP:

Intraperitoneal injection

ICV:

Intracerebroventricular injection

LV:

Left ventricle

LVEF:

LV ejection fraction

LVEDV:

LV end-diastolic volume

LVEDP:

Left ventricular end-diastolic pressure

mPVN:

Magnocellular PVN

MI:

Myocardial infarction

NE:

Norepinephrine

PVN:

Hypothalamic paraventricular nucleus

PICs:

Pro-inflammatory cytokines

PGE2 :

Prostaglandin E2.

RSNA:

Renal sympathetic nerve activity

RV:

Right ventricle

SHAM:

Sham-operated control

SNP:

Sodium nitroprusside

TNF:

Tumour necrosis factor

TH:

Tyrosine hydroxylase

vlpPVN:

Ventrolateral parvocellular PVN

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Acknowledgments

Funding: Supported by National Natural Science Foundation of China (No. 81070199), US National Institutes of Health (NIH) Grant RO1-HL-080544-01, and Fundamental Research Funds for the Central Universities of China (No. 08142001).

Conflict of interest

None declared.

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Authors and Affiliations

  1. Department of Physiology and Pathophysiology, Xi’an Jiaotong University School of Medicine, Xi’an, 710061, China

    Yu-Ming Kang

  2. Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70803, USA

    Jeffrey P. Cardinale, Carrie Elks & Joseph Francis

  3. Department of Physiology, Shanxi Medical University, Taiyuan, China

    Xi-Mei Cao

  4. Institute of Hepatobiliary Surgery, General Hospital of Chinese People’s Liberation Army, Beijing, China

    Ai-Qun Zhang

  5. Department of Internal Medicine, General Hospital of Chinese People’s Armed Police Forces, Beijing, China

    Xiu-Fang Zhao & Zhen-Wen Zhang

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  1. Yu-Ming Kang
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Correspondence to Yu-Ming Kang or Joseph Francis.

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Y.-M. Kang, A.-Q. Zhang and X.-F. Zhao contributed equally to this study.

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Kang, YM., Zhang, AQ., Zhao, XF. et al. Paraventricular nucleus corticotrophin releasing hormone contributes to sympathoexcitation via interaction with neurotransmitters in heart failure. Basic Res Cardiol 106, 473–483 (2011). https://doi.org/10.1007/s00395-011-0155-2

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