Central proopiomelanocortin but not neuropeptide Y mediates sympathoexcitation and hypertension in fat fed conscious rabbits

Barzel, Benjamin, Lim, Kyungjoon, Davern, Pamela J., Burke, Sandra L., Armitage, James A. and Head, Geoffrey A. 2016, Central proopiomelanocortin but not neuropeptide Y mediates sympathoexcitation and hypertension in fat fed conscious rabbits, Journal of hypertension, vol. 34, no. 3, pp. 464-473, doi: 10.1097/HJH.0000000000000811.

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Title Central proopiomelanocortin but not neuropeptide Y mediates sympathoexcitation and hypertension in fat fed conscious rabbits
Author(s) Barzel, Benjamin
Lim, Kyungjoon
Davern, Pamela J.
Burke, Sandra L.
Armitage, James A.ORCID iD for Armitage, James A. orcid.org/0000-0002-3762-0911
Head, Geoffrey A.
Journal name Journal of hypertension
Volume number 34
Issue number 3
Start page 464
End page 473
Total pages 10
Publisher Lippincott Williams & Wilkins
Place of publication Philadelphia, Pa.
Publication date 2016-03
ISSN 1473-5598
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Peripheral Vascular Disease
Cardiovascular System & Cardiology
-melanocortin stimulating hormone
hypertension
leptin
neuropeptide Y
obesity
renal sympathetic nerve activity
SYMPATHETIC-NERVE ACTIVITY
SELECTIVE LEPTIN RESISTANCE
DIET-INDUCED OBESE
DORSOMEDIAL HYPOTHALAMUS
ARTERIAL-PRESSURE
BLOOD-PRESSURE
PARAVENTRICULAR NUCLEUS
MELANOCORTIN SYSTEM
ANGIOTENSIN-II
RISK-FACTORS
Summary OBJECTIVE: High-fat diet (HFD)-induced hypertension in rabbits is neurogenic because of the central sympathoexcitatory actions of leptin. Hypothalamic melanocortin and neuropeptide Y (NPY) neurons are recognized as the major signalling pathways through which leptin exerts its central effects. In this study, we assessed the effects of specific antagonists and agonists to melanocortin and NPY receptors on HFD-induced sympathoexcitation and hypertension. METHODS: Rabbits were instrumented with intracerebroventricular cannula, renal sympathetic nerve activity (RSNA) electrode, and blood pressure telemetry transmitter. RESULTS: After 3 weeks HFD (13.5% fat, n = 12) conscious rabbits had higher RSNA (+3.8  nu, P = 0.02), blood pressure (+8.6  mmHg, P < 0.001) and heart rate (+15  b/min, P = 0.01), and brain-derived neurotrophic factor levels in the hypothalamus compared with rabbits fed a control diet (4.2% fat, n = 11). Intracerebroventricular administration of the melanocortin receptor antagonist SHU9119 reduced RSNA (-2.7  nu) and blood pressure (-8.5  mmHg) in HFD but not control rabbits, thus reversing 100% of the hypertension and 70% of the sympathoexcitation induced by a HFD. By contrast, blocking central NPY Y1 receptors with BVD10 increased RSNA only in HFD rabbits. Intracerebroventricular α-melanocortin stimulating hormone increased RSNA and heart rate (P < 0.001) in HFD rabbits but had no effect in control rabbits. CONCLUSION: These findings suggest that obesity-induced hypertension and increased RSNA are dependent on the balance between greater activation of melanocortin signalling through melanocortin receptors and lesser activation of NPY sympathoinhibitory signalling. The amplification of the sympathoexcitatory effects of α-melanocortin stimulating hormone also indicates that the underlying mechanism is related to facilitation of leptin-melanocortin signalling, possibly involving chronic activation of brain-derived neurotrophic factor.
Language eng
DOI 10.1097/HJH.0000000000000811
Field of Research 110306 Endocrinology
110201 Cardiology (incl Cardiovascular Diseases)
1103 Clinical Sciences
1102 Cardiovascular Medicine And Haematology
Socio Economic Objective 920103 Cardiovascular System and Diseases
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Wolters Kluwer Health, Inc.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30082605

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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