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Origin of Aberrant Blood Pressure and Sympathetic Regulation in Diet-Induced Obesity
journal contribution
posted on 2016-08-01, 00:00 authored by K Lim, B Barzel, S L Burke, James ArmitageJames Armitage, G A HeadHigh 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.
History
Journal
HypertensionVolume
68Issue
2Pagination
491 - 500Publisher DOI
ISSN
0194-911XeISSN
1524-4563Publication classification
C Journal article; C1 Refereed article in a scholarly journalCopyright notice
2016, American Heart AssociationUsage metrics
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No categories selectedKeywords
Science & TechnologyLife Sciences & BiomedicinePeripheral Vascular DiseaseCardiovascular System & Cardiologyhypertensionleptinneuropeptide YobesitySHU9119NEUROPEPTIDE-YDORSOMEDIAL HYPOTHALAMUSINDUCED HYPERTENSIONNERVE ACTIVITYPARAVENTRICULAR NUCLEUSMELANOCORTIN SYSTEMARCUATE NUCLEUSZUCKER RATSRABBITS
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