title: P2X7 deficiency attenuates hypertension and renal injury in deoxycorticosterone acetate-salt hypertension.
abstract: The P2X(7) receptor is a ligand-gated ion channel, and genetic variations in the P2X(7) gene significantly affect blood pressure. P2X(7) receptor expression is associated with renal injury and inflammatory diseases. Uninephrectomized wild-type (WT) and P2X(7)-deficient (P2X(7) 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, P2X(7) mRNA and protein expression increased in WT mice. Blood pressure in P2X(7) 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 P2X(7) KO mice than in WT mice (0.11 ± 0.07 vs. 0.28 ± 0.07 mg/day). Creatinine clearance was higher in P2X(7) 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 P2X(7) KO mice compared with WT mice. The levels of IL-1β, released by macrophages, in P2X(7) KO mice had decreased dramatically compared with that in WT mice. These results strongly suggest that the P2X(7) receptor plays a key role in the development of hypertension and renal disease via increased inflammation, indicating its potential as a novel therapeutic target.
authors.affiliation: Dept. of Genomic Medicine, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka, Japan.
authors.forename: Xu
authors.initials: X
authors.lastname: Ji
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Naito
authors.forename: Huachun
authors.initials: H
authors.lastname: Weng
authors.forename: Kosuke
authors.initials: K
authors.lastname: Endo
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.forename: Naoharu
authors.initials: N
authors.lastname: Iwai
mesh_terms: D000419:Albuminuria / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003900:Desoxycorticosterone / Q000493:pharmacokinetics*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D053583:Interleukin-1beta / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058486:Receptors, Purinergic P2X7 / Q000235:genetics* / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*
chemical_list: D053583:Interleukin-1beta; D058486:Receptors, Purinergic P2X7; D017673:Sodium Chloride, Dietary; D003900:Desoxycorticosterone