Hypertensive Nephropathy: Unveiling the Possible Involvement of Hemichannels and Pannexons

• Published in: International journal of molecular sciences 2022-12, Vol.23 (24), p.15936
• Main Authors: Lucero, Claudia M, Prieto-Villalobos, Juan, Marambio-Ruiz, Lucas, Balmazabal, Javiera, Alvear, Tanhia F, Vega, Matías, Barra, Paola, Retamal, Mauricio A, Orellana, Juan A, Gómez, Gonzalo I
• Format: Article
• Language: English
• Subjects: Adenosine; Angiotensin; Angiotensin II; Animals; Blood flow; Blood pressure; Calcium (intracellular); Calcium channels; Calcium ions; Calcium signalling; Cardiovascular disease; Cardiovascular diseases; Cell activation; Channels; Chemokines; Chronic illnesses; connexin 43 hemichannel; Connexins; Connexins - physiology; Cytokines; Deregulation; Electrolytes; Extracellular matrix; Fibrosis; gap junctions; Gap Junctions - physiology; Glomerulus; Homeostasis; Humans; Hypertension; Hypertension, Renal; hypertensive nephropathy; Inflammation; Intracellular signalling; Kidney diseases; Mesangial cells; Nephritis; Nephropathy; Oxidative stress; pannexins 1 channels; Pathogenesis; Proteins; Purine receptors; Review; Risk analysis; Risk factors; Tumor necrosis factor-TNF; Vasoactive agents; Vertebrates
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232415936

Hypertension is one of the most common risk factors for developing chronic cardiovascular diseases, including hypertensive nephropathy. Within the glomerulus, hypertension causes damage and activation of mesangial cells (MCs), eliciting the production of large amounts of vasoactive and proinflammatory agents. Accordingly, the activation of AT1 receptors by the vasoactive molecule angiotensin II (AngII) contributes to the pathogenesis of renal damage, which is mediated mostly by the dysfunction of intracellular Ca ([Ca ] ) signaling. Similarly, inflammation entails complex processes, where [Ca ] also play crucial roles. Deregulation of this second messenger increases cell damage and promotes fibrosis, reduces renal blood flow, and impairs the glomerular filtration barrier. In vertebrates, [Ca ] signaling depends, in part, on the activity of two families of large-pore channels: hemichannels and pannexons. Interestingly, the opening of these channels depends on [Ca ] signaling. In this review, we propose that the opening of channels formed by connexins and/or pannexins mediated by AngII induces the ATP release to the extracellular media, with the subsequent activation of purinergic receptors. This process could elicit Ca overload and constitute a feed-forward mechanism, leading to kidney damage.