The P2Y6 Receptor as a Potential Keystone in Essential Hypertension.

Function (Oxf)

Departamento de Bioquímica y Biología Molecular y Fisiología e Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid y Consejo Superior de Investigaciones Científicas (CSIC), Valladolid, 47003, Spain.

Published: November 2024

Essential hypertension (HT) is a highly prevalent cardiovascular disease of unclear physiopathology. Pharmacological studies suggest that purinergic P2Y6 receptors (P2ry6) play important roles in cardiovascular function and may contribute to angiotensin II (AgtII) pathophysiological effects. Here, we tested the hypothesis that functional coupling between P2ry6 and AgtII receptors mediates altered vascular reactivity in HT. For this, a multipronged approach was implemented using mesenteric vascular smooth muscle cells (VSMCs) and arteries from Blood Pressure Normal (BPN) and Blood Pressure High (BPH) mice. Differential transcriptome profiling of mesenteric artery VSMCs identified P2ry6 purinergic receptor mRNA as one of the top upregulated transcripts in BPH. P2Y receptor activation elicited distinct vascular responses in mesenteric arteries from BPN and BPH mice. Accordingly, 10 µm UTP produced a contraction close to half-maximal activation in BPH arteries but no response in BPN vessels. AgtII-induced contraction was also higher in BPH mice despite having lower AgtII receptor type-1 (Agtr1) expression and was sensitive to P2ry6 modulators. Proximity ligation assay and super-resolution microscopy showed closer localization of Agtr1 and P2ry6 at/near the membrane of BPH mice. This proximal association was reduced in BPN mice, suggesting a functional role for Agtr1-P2ry6 complexes in the hypertensive phenotype. Intriguingly, BPN mice were resistant to AgtII-induced HT and showed reduced P2ry6 expression in VSMCs. Altogether, results suggest that increased functional coupling between P2ry6 and Agtr1 may contribute to enhanced vascular reactivity during HT. In this regard, blocking P2ry6 could be a potential pharmacological strategy to treat HT.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577605PMC
http://dx.doi.org/10.1093/function/zqae045DOI Listing

Publication Analysis

Top Keywords

bph mice
16
essential hypertension
8
p2ry6
8
functional coupling
8
coupling p2ry6
8
vascular reactivity
8
blood pressure
8
bpn mice
8
bph
6
mice
6

Similar Publications

The aim is to explore the mechanisms underlying pain development in chronic prostatitis and identify therapeutic targets for pain management in patients with chronic prostatitis. RNA sequence of the spinal cord dorsal horns and proteomic analysis of spinal macrophages of experimental autoimmune prostatitis (EAP) mice were conducted to identify pain-related genes, proteins and signalling pathways. The clodronate liposome, CXCR3 and P-STAT3 inhibitors, NGF antibody and cromolyn sodium were used to investigate the roles of the CXCL10/CXCR3, JAK/STAT3 and NGF/TrKA pathways in spinal macrophage recruitment and pain response.

View Article and Find Full Text PDF

Benign prostatic hyperplasia (BPH) is an age-related disease that affects millions of aging males globally. While the pathogenesis of BPH remains incompletely understood, emerging evidence suggests a pivotal role for the androgen receptor (AR) in mediating prostate growth and function. Understanding age-related AR signaling alteration may inform novel BPH treatments.

View Article and Find Full Text PDF

A sex-dependent role of Kv1.3 channels from macrophages in metabolic syndrome.

Front Physiol

November 2024

Departamento de Bioquímica y Biología Molecular y Fisiología, Universidad de Valladolid, Valladolid, Spain.

Article Synopsis
  • Coronary artery disease (CAD) is a leading cause of death and disability worldwide, particularly affecting patients with type 2 diabetes (T2DM) who experience worse outcomes due to inflammation and endothelial dysfunction.* ! -
  • The study investigates the role of K1.3 channel blockers in reducing intimal hyperplasia and improving metabolic dysfunction in a T2DM mouse model, focusing on the macrophage K1.3 channels as potential therapeutic targets.* ! -
  • Results indicate that K1.3 channel expression is increased in macrophages from T2DM mice, especially in females, but these channels primarily influence cell migration rather than metabolic function or phagocytosis.* !
View Article and Find Full Text PDF

Microglial activation without peripheral immune cell infiltration characterises mouse and human cerebral small vessel disease.

Neuropathol Appl Neurobiol

December 2024

Institute of Physiological Chemistry and Pathobiochemistry and Cells-in-Motion Interfaculty Centre (CiMIC), University of Muenster, Muenster, Germany.

Aims: Cerebral small vessel diseases (SVDs) involve diverse pathologies of the brain's small blood vessels, leading to cognitive deficits. Cerebral magnetic resonance imaging (MRI) reveals white matter hyperintensities (WMHs), lacunes, microbleeds and enlarged perivascular spaces in SVD patients. Although correlations of MRI and histopathology help to understand the pathogenesis of SVD, they do not explain disease progression.

View Article and Find Full Text PDF

Background And Purpose: MicroRNA (miRNA) therapy is a promising approach to induce cardioprotection. We have previously identified cardiac microRNA-125b* (microRNA-125b-2-3p; miR-125b*) as a potential cardioprotective miRNA, termed ProtectomiR. We aimed to characterize the pharmacokinetics and pharmacodynamics, and the effect of miR-125b* mimic on infarct size using an in vivo mouse model.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!