ArticleMolecular metabolism2016
Mechanisms underlying prorenin actions on hypothalamic neurons implicated in cardiometabolic control.
Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Cellular and Molecular Architecture of Renin-Angiotensin System Signaling in the PVN Under Cardiometabolic Stress.bioRxiv : the preprint server for biology · 2025Article
- (Pro)renin receptor signaling in hypothalamic tyrosine hydroxylase neurons is required for obesity-associated glucose metabolic impairment.JCI insight · 2024Article
- The hypothalamus as a key regulator of glucose homeostasis: emerging roles of the brain renin-angiotensin system.American journal of physiology. Cell physiology · 2023Review
- Cardiovascular Neuroendocrinology: Emerging Role for Neurohypophyseal Hormones in Pathophysiology.Endocrinology · 2021Review
- Increased (Pro)renin Receptor Expression in the Hypertensive Human Brain.Frontiers in physiology · 2020Article
- The (pro)renin receptor in health and disease.Nature reviews. Nephrology · 2019Review
- Exacerbated effects of prorenin on hypothalamic magnocellular neuronal activity and vasopressin plasma levels during salt-sensitive hypertension.American journal of physiology. Heart and circulatory physiology · 2019Article
- (Pro)renin receptor knockdown in the paraventricular nucleus of the hypothalamus attenuates hypertension development and ATAmerican journal of physiology. Heart and circulatory physiology · 2019Article
- The renin-angiotensin system in cardiovascular autonomic control: recent developments and clinical implications.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2019Review
- The prorenin receptor in the cardiovascular system and beyond.American journal of physiology. Heart and circulatory physiology · 2018Review
- A-type KAmerican journal of physiology. Heart and circulatory physiology · 2017Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHypertension and obesity are highly interrelated diseases, being critical components of the metabolic syndrome. Despite the growing prevalence of this syndrome in the world population, efficient therapies are still missing. Thus, identification of novel targets and therapies are warranted. An enhanced activity of the hypothalamic renin-angiotensin system (RAS), including the recently discovered prorenin (PR) and its receptor (PRR), has been implicated as a common mechanism underlying aberrant sympatho-humoral activation that contributes to both metabolic and cardiovascular dysregulation in the metabolic syndrome. Still, the identification of precise neuronal targets, cellular mechanisms and signaling pathways underlying PR/PRR actions in cardiovascular- and metabolic related hypothalamic nuclei remain unknown. METHODS AND
resultsUsing a multidisciplinary approach including patch-clamp electrophysiology, live calcium imaging and immunohistochemistry, we aimed to elucidate cellular mechanisms underlying PR/PRR actions within the hypothalamic supraoptic (SON) and paraventricular nucleus (PVN), key brain areas previously involved in cardiometabolic regulation. We show for the first time that PRR is expressed in magnocellular neurosecretory cells (MNCs), and to a lesser extent, in presympathetic PVN neurons (PVNPS). Moreover, we show that while PRR activation efficiently stimulates the firing activity of both MNCs and PVNPS neurons, these effects involved AngII-independent and AngII-dependent mechanisms, respectively. In both cases however, PR excitatory effects involved an increase in intracellular Ca(2+) levels and a Ca(2+)-dependent inhibition of a voltage-gated K(+) current.
conclusionsWe identified novel neuronal targets and cellular mechanisms underlying PR/PRR actions in critical hypothalamic neurons involved in cardiometabolic regulation. This fundamental mechanistic information regarding central PR/PRR actions is essential for the development of novel RAS-based therapeutic targets for the treatment of cardiometabolic disorders in obesity and hypertension.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.