Journal article
Activation of hypothalamic AgRP and POMC neurons evokes disparate sympathetic and cardiovascular responses
American journal of physiology. Heart and circulatory physiology, Vol.319(5), pp.H1069-H1077
11/01/2020
DOI: 10.1152/AJPHEART.00411.2020
PMCID: PMC7789969
PMID: 32946297
Abstract
The arcuate nucleus of the hypothalamus (ARC) plays a key role in linking peripheral metabolic status to the brain melanocortin system, which influences a wide range of physiological processes including the sympathetic nervous system and blood pressure. The importance of the activity of agouti-related peptide (AgRP)- and proopiomelanocortin (POMC)-expressing neurons, two molecularly distinct populations of ARC neurons, for metabolic regulation is well established, but their relevance for sympathetic and cardiovascular control remains unclear. We used designer receptors exclusively activated by designer drug (DREADD) technology to study how activation of AgRP and POMC neurons affect renal sympathetic nerve traffic and blood pressure. In addition to the drastic feeding-stimulatory effect, DREADD-mediated activation of AgRP, but not POMC neurons, induced an acute reduction in renal sympathetic nerve activity in conscious mice. Paradoxically, however, DREADD-mediated chronic activation of AgRP neurons caused a significant increase in blood pressure specifically in the inactive light phase. On the other hand, chronic activation of POMC neurons led to a significant reduction in blood pressure. These results bring new insights to a previously unappreciated role of ARC AgRP and POMC neuronal activity in autonomic and cardiovascular regulation.\nAgouti-related peptide (AgRP)- and proopiomelanocortin (POMC)-expressing neurons of the arcuate nucleus are essential components of the brain melanocortin system that controls various physiological processes. Here, we tested the metabolic and cardiovascular effects of direct activation of these two populations of neurons. Our findings show that, in addition to stimulation of food intake, chemogenetic mediated activation of hypothalamic arcuate nucleus AgRP, but not POMC, neurons reduce renal sympathetic traffic. Despite this, chronic activation of AgRP neurons increased blood pressure. However, chronic activation of POMC neurons led to a significant reduction in blood pressure. Our findings highlight the importance of arcuate nucleus AgRP and POMC neuronal activity in autonomic and cardiovascular regulation.
Details
- Title: Subtitle
- Activation of hypothalamic AgRP and POMC neurons evokes disparate sympathetic and cardiovascular responses
- Creators
- Jingwei Jiang - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IowaDonald A Morgan - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IowaHuxing Cui - Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IowaKamal Rahmouni - Veterans Affairs Health Care System, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.319(5), pp.H1069-H1077
- Publisher
- United States
- DOI
- 10.1152/AJPHEART.00411.2020
- PMID
- 32946297
- PMCID
- PMC7789969
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Grant note
- 5T32HL007344 / HHS | National Institutes of Health (NIH)\nT32 HL007344 / NHLBI NIH HHS\nT32 DK112751 / NIDDK NIH HHS\n5T32DK112751 / HHS | National Institutes of Health (NIH)\nHL127673 / HHS | National Institutes of Health (NIH)\nMH109920 / HHS | National Institutes of Health (NIH)\nR21 MH109920 / NIMH NIH HHS\nP01 HL084207 / NHLBI NIH HHS\nR01 HL127673 / NHLBI NIH HHS\nI01 BX004249 / BLRD VA
- Language
- English
- Date published
- 11/01/2020
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984070237902771
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