Origin of Aberrant Blood Pressure and Sympathetic Regulation in Diet-Induced Obesity. Issue 2 (August 2016)

• Record Type: Journal Article
• Authors: Lim, Kyungjoon; Barzel, Benjamin; Burke, Sandra L.; Armitage, James A.; Head, Geoffrey A.
• Is Part Of: Hypertension. Volume 68:Issue 2(2016:Aug.)
• Publication Date: 2016-08
• Subjects: hypertension -- leptin -- neuropeptide Y -- obesity -- SHU9119; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.116.07461
• Languages: English
• ISSNs: 0194-911X

Abstract

Abstract : 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. Abstract : Supplemental Digital Content is available in the text.