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The P2Y6 Receptor as a Potential Keystone in Essential Hypertension
Nuria Daghbouche-Rubio1, Inés Álvarez-Miguel1, Victor Alejandro Flores2
1Departamento 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.
Function (Oxford, England)
|September 25, 2024
Summary
Essential hypertension involves unclear mechanisms. This study reveals that increased P2Y6 receptor (P2ry6) and angiotensin II receptor (Agtr1) coupling enhances vascular reactivity in hypertension, suggesting P2ry6 as a potential therapeutic target.
Area of Science:
- Cardiovascular Research
- Molecular Pharmacology
- Hypertension Pathophysiology
Background:
- Essential hypertension (HT) is a widespread cardiovascular disease with poorly understood mechanisms.
- Purinergic P2Y6 receptors (P2ry6) are implicated in cardiovascular function and angiotensin II (AgtII) effects.
Purpose of the Study:
- To investigate the hypothesis that functional coupling between P2ry6 and AgtII receptors contributes to altered vascular reactivity in HT.
- To explore the role of P2ry6 in the hypertensive phenotype.
Main Methods:
- Transcriptome profiling of mesenteric vascular smooth muscle cells (VSMCs) from normal and hypertensive mice.
- Assessment of vascular responses to P2Y receptor activation and AgtII.
- Proximity ligation assay and super-resolution microscopy to determine receptor localization.
Main Results:
- P2ry6 mRNA was upregulated in hypertensive mouse mesenteric arteries.
- Hypertensive mice showed enhanced vascular contraction to UTP and AgtII, with AgtII-induced contraction sensitive to P2ry6 modulators.
- Agtr1 and P2ry6 receptors exhibited closer proximity at the cell membrane in hypertensive mice.
Conclusions:
- Increased functional coupling between P2ry6 and Agtr1 may drive enhanced vascular reactivity in hypertension.
- Reduced P2ry6 expression correlated with resistance to AgtII-induced hypertension.
- Blocking P2ry6 presents a potential therapeutic strategy for treating hypertension.
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