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Activation of hypothalamic AgRP and POMC neurons evokes disparate sympathetic and cardiovascular responses. | LitMetric

AI Article Synopsis

  • The arcuate nucleus of the hypothalamus (ARC) is crucial for linking body metabolism to the brain's melanocortin system, affecting processes like blood pressure and sympathetic nervous system activity.
  • Using DREADD technology, researchers found that activating AgRP neurons decreased renal sympathetic nerve activity, while chronic activation of these neurons led to an increase in blood pressure during the light phase.
  • Conversely, chronic activation of POMC neurons resulted in a significant decrease in blood pressure, highlighting the different roles of AgRP and POMC neurons in cardiovascular regulation.

Article 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. Agouti-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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789969PMC
http://dx.doi.org/10.1152/ajpheart.00411.2020DOI Listing

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