P2X(7) receptor antagonism attenuates the hypertension and renal injury in Dahl salt-sensitive rats. 2012

Xu Ji, and Yukiko Naito, and Go Hirokawa, and Huachun Weng, and Yumiko Hiura, and Rie Takahashi, and Naoharu Iwai
Department of Genomic Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.

The P2X(7) receptor is a ligand-gated ion channel activated by extracellular ATP, and a common genetic variation in the P2X(7) gene significantly affects blood pressure. P2X(7) receptor expression is associated with renal injury and some inflammatory diseases. Brilliant blue G (BBG) is a selective rat P2X(7) receptor antagonist. In this study, to test whether BBG has protective effects on salt-sensitive hypertension and renal injury, Dahl salt-sensitive (DS) rats fed an 8% NaCl diet were i.p. injected with BBG (50 mg kg(-1) per day) for 4 weeks. We also tested another P2X(7) receptor antagonist, namely A-438079 (100 mg kg(-1) per day), for 7 days. We found that P2X(7) antagonism markedly attenuated salt-sensitive hypertension, urinary protein or albumin excretion, renal interstitial fibrosis and macrophage and T-cell infiltration in the DS rats, and significantly improved creatinine clearance. In an in vitro experiment using macrophages, we showed that lipopolysaccharide (LPS)-primed macrophages from the DS rats released more interleukin-1 beta in response to BzATP, a P2X(7) receptor agonist, than the macrophages from Lewis rats, possibly due to higher P2X(7) expression in the DS rats. In conclusion, in vivo blockade of P2X(7) receptors attenuated salt-sensitive hypertension and renal injury in the DS rats. Thus, P2X(7) appears to be responsible for a vicious cycle of salt-sensitive hypertension and renal injury in the DS rats, through higher expression in the immune cells. Furthermore, P2X(7) antagonists can prevent the development of salt-sensitive hypertension and renal injury, thus confirming that the P2X(7) receptor is an important therapeutic target.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007674 Kidney Diseases Pathological processes of the KIDNEY or its component tissues. Disease, Kidney,Diseases, Kidney,Kidney Disease
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D011917 Rats, Inbred Lew An inbred strain of rat that is used in BIOMEDICAL RESEARCH. Rats, Inbred Lewis,Rats, Lew,Inbred Lew Rat,Inbred Lew Rats,Inbred Lewis Rats,Lew Rat,Lew Rat, Inbred,Lew Rats,Lew Rats, Inbred,Lewis Rats, Inbred,Rat, Inbred Lew,Rat, Lew
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000419 Albuminuria The presence of albumin in the urine, an indicator of KIDNEY DISEASES. Albuminurias

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