P2X7 deficiency attenuates hypertension and renal injury in deoxycorticosterone acetate-salt hypertension

The P2X7 receptor is a ligand-gated ion channel, and genetic variations in the P2X7 gene significantly affect blood pressure. P2X7 receptor expression is associated with renal injury and inflammatory diseases. Uninephrectomized wild-type (WT) and P2X7-deficient (P2X7 KO) mice were subcutaneously implanted with deoxycorticosterone acetate (DOCA) pellets and fed an 8% salt diet for 18 days. Their blood pressure was assessed by a telemetry system. The mice were placed in metabolic cages, and urine was collected for 24 h to assess renal function. After 18 days of DOCA-salt treatment, P2X7 mRNA and protein expression increased in WT mice. Blood pressure in P2X7 KO mice was less than that of WT mice (mean systolic blood pressure 133 ± 3 vs. 150 ± 2 mmHg). On day 18 , urinary albumin excretion was lower in P2X7 KO mice than in WT mice (0.11 ± 0.07 vs. 0.28 ± 0.07 mg/day). Creatinine clearance was higher in P2X7 KO mice than in WT mice (551.53 ± 65.23 vs. 390.85 ± 32.81 μl·min−1·g renal weight−1). Moreover, renal interstitial fibrosis and infiltration of immune cells (macrophages, T cells, B cells, and leukocytes) were markedly attenuated in P2X7 KO mice compared with WT mice. The levels of IL-1β, released by macrophages, in P2X7 KO mice had decreased dramatically compared with that in WT mice. These results strongly suggest that the P2X7 receptor plays a key role in the development of hypertension and renal disease via increased inflammation, indicating its potential as a novel therapeutic target.