Vasoactive effects of P2X7 receptors in the aorta of control and hypertensive mice

Amelia Howarth, Robert Menzies, Bryan Conway, Matthew Bailey

Research output: Contribution to conferenceAbstract

Abstract / Description of output

P2X7 receptors (P2X7R) are activated by extracellular ATP and have well defined pro-inflammatory roles in immune cells. The receptor is also expressed in the vascular endothelium and we recently reported that systemic infusion of a P2X7R antagonist reduced blood pressure and increased renal perfusion in hypertensive rats (Menzies et al, Kidney International, 88, p1079, 2015). In the present study we performed a comprehensive immunlocalisation study of P2X7R expression in the mouse renal vasculature and examined the effect of P2X7R activation on the contractility of isolated aorta.

Kidneys from male C57BL6 mice were fixed and P2X7R immunofluorescence performed using a rabbit anti-P2X7 primary antibody (Alomone, 1:500). Immunofluorescence staining was also performed using antibodies against CD31 (endothelium marker); αSMA (vascular smooth muscle marker) and PDGFRβ (pericyte marker). This approach localised P2X7 to the endothelium of mouse renal arteries and glomerular capillaries, but not to the vascular smooth muscle. P2X7 was also seen to co-localise with PDGFRβ at focal points in the renal medulla.

To examine the functional role of vascular P2XR7 expression, we performed wire myography on thoracic aorta dissected from male C57BL6 mice (n=5). The P2X7R agonist, BzATP (50μM) induced a modest vasoconstriction, amounting to 20±5.2% of that induced by depolarisation with KCL. Preincubation with the P2X7R antagonist A438079 (10μM), blocked ~70% of the BZATP-induced constriction.

In a separate group of mice, we induced hypertension (Hypertensive mice: 136.5±3.2mmHg Control mice: 113.3±1.9mmHg) through a 4 week administration of ANGII (100ng/kg/min) and deoxycorticosterone (50mg), combined with high salt feeding. This regimen induced perivascular fibrosis but no albuminuria. In this setting, BZATP also induced a constriction, similar to that observed in non-treated mice. However, pre-incubation with the P2X7R antagonist amplified the constrictive response to BZATP.

Our data confirm endothelial expression of P2X7R innormotensive mice and suggest that activation of the receptor exerts a modest vasoconstriction. In hypertensive animals, our data suggest that P2X7R exerts a vasodilatory tone.
Original languageEnglish
Publication statusPublished - 2017


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