Origin of aberrant blood pressure and sympathetic regulation in diet-induced obesity

Lim, Kyungjoon, Barzel, Benjamin, Burke, Sandra L., Armitage, James A. and Head, Geoffrey A. 2016, Origin of aberrant blood pressure and sympathetic regulation in diet-induced obesity, Hypertension, vol. 68, no. 2, pp. 491-500, doi: 10.1161/HYPERTENSIONAHA.116.07461.

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Title Origin of aberrant blood pressure and sympathetic regulation in diet-induced obesity
Author(s) Lim, Kyungjoon
Barzel, Benjamin
Burke, Sandra L.
Armitage, James A.ORCID iD for Armitage, James A. orcid.org/0000-0002-3762-0911
Head, Geoffrey A.
Journal name Hypertension
Volume number 68
Issue number 2
Start page 491
End page 500
Total pages 10
Publisher American heart association
Place of publication Dallas, Tex.
Publication date 2016-08
ISSN 1524-4563
Keyword(s) SHU9119
neuropeptide Y
Science & Technology
Life Sciences & Biomedicine
Peripheral Vascular Disease
Cardiovascular System & Cardiology
Summary High fat diet (HFD)-induced hypertension in rabbits is neurogenic and caused by the central action of leptin, which is thought to be dependent on activation of α-melanocortin-stimulating hormone (α-MSH) and neuropeptide Y-positive neurons projecting to the dorsomedial hypothalamus (DMH) and ventromedial hypothalamus (VMH). However, leptin may act directly in these nuclei. Here, we assessed the contribution of leptin, α-MSH, and neuropeptide Y signaling in the DMH and VMH to diet-induced hypertension. Male New Zealand white rabbits were instrumented with a cannula for drug injections into the DMH or VMH and a renal sympathetic nerve activity (RSNA) electrode. After 3 weeks of an HFD (13.3% fat; n=19), rabbits exhibited higher RSNA, mean arterial pressure (MAP), and heart rate compared with control diet-fed animals (4.2% fat; n=15). Intra-VMH injections of a leptin receptor antagonist or SHU9119, a melanocortin 3/4 receptor antagonist, decreased MAP, heart rate, and RSNA compared with vehicle in HFD rabbits (P<0.05) but not in control diet-fed animals. By contrast, α-MSH or neuropeptide Y injected into the VMH had no effect on MAP but produced sympathoexcitation in HFD rabbits (P<0.05) but not in control diet-fed rabbits. The effects of the leptin antagonist, α-MSH, or neuropeptide Y injections into the DMH on MAP or RSNA of HFD rabbits were not different from those after vehicle injection. α-MSH into the DMH of control diet-fed animals did increase MAP, heart rate, and RSNA. We conclude that the VMH is the likely origin of leptin-mediated sympathoexcitation and α-MSH hypersensitivity that contribute to obesity-related hypertension.
Language eng
DOI 10.1161/HYPERTENSIONAHA.116.07461
Field of Research 111799 Public Health and Health Services not elsewhere classified
1103 Clinical Sciences
1102 Cardiovascular Medicine And Haematology
Socio Economic Objective 920499 Public Health (excl. Specific Population Health) not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, American Heart Association
Persistent URL http://hdl.handle.net/10536/DRO/DU:30085971

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