title: Microglial P2X₇ receptor in the hypothalamic paraventricular nuclei contributes to sympathoexcitatory responses in acute myocardial infarction rat.
abstract: Several pieces of evidence indicate that the microglial P2X7 receptor (P2X7R) regulate cardiovascular activities. We explored the possible roles of microglial P2X7R in the PVN mediated sympathoexcitatory responses in acute myocardial infarction (AMI) rat. Sprague-Dawley rats underwent coronary artery ligation to induce AMI. The rats received intraperitoneal administration of the P2X7R antagonist Brilliant Blue-G (BBG, 25 or 50 mg kg(-1), once a day for 5 days) prior to myocardial ischemia. Other rats received bilateral microinjection of P2X7R-siRNA (0.015 or 0.03 nmol 0.1μl per side, once a day for 2 days) targeting P2X7R mRNA into the PVN prior to myocardial ischemia. First, we examined the ATP levels and protein expression P2X7R in the PVN in different ischemia time groups, and we found that the change of P2X7R was positive correlated with the ATP levels in a time-dependent manner. The double-immunofluorescence evidence showed that P2X7R was mainly co-localizated with the microglial marker Iba-1 in the PVN. Second, gene knockdown of P2X7R with P2X7-siRNA or inhibition of P2X7R with BBG reduce the mRNA and protein expression of IL-1β and TNF-α in the PVN of AMI rat. Third, microinjected P2X7-siRNA also suppressed the up-regulation of P2X7R, oxytocin and vasopressin in the PVN of AMI rats. Fourth, P2X7-siRNA and BBG also attenuated the renal sympathetic nerve activity (RSNA) in the AMI rats. Our results indicate that microglial P2X7R activation in PVN mediating the production of proinflammatory cytokines that activate oxytocinergic and vasopressinergic neuron, which augmented the RSNA in the AMI rat.
authors.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, PR China.
authors.forename: Dongshu
authors.initials: D
authors.lastname: Du
authors.affiliation: Oregon Hearing Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, 138 Yixueyuan Road, Shanghai 200032, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, 138 Yixueyuan Road, Shanghai 200032, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, 138 Yixueyuan Road, Shanghai 200032, PR China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Xia
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, 138 Yixueyuan Road, Shanghai 200032, PR China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Guan
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, 138 Yixueyuan Road, Shanghai 200032, PR China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Shen
authors.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, PR China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, 138 Yixueyuan Road, Shanghai 200032, PR China. Electronic address: sdhzdds@126.com.
authors.forename: Danian
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001794:Blood Pressure; D002135:Calcium-Binding Proteins / Q000378:metabolism; D006339:Heart Rate; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism*; D012394:Rosaniline Dyes / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism
chemical_list: C100745:Aif1 protein, rat; D034961:Antigens, Nuclear; D002135:Calcium-Binding Proteins; D053583:Interleukin-1beta; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D058920:Purinergic P2X Receptor Antagonists; D034741:RNA, Small Interfering; C546339:Rbfox3 protein, rat; D058486:Receptors, Purinergic P2X7; D012394:Rosaniline Dyes; D014409:Tumor Necrosis Factor-alpha; D014667:Vasopressins; D010121:Oxytocin; D000255:Adenosine Triphosphate; C004692:coomassie Brilliant Blue
keywords: Acute myocardial infarction; Hypothalamic paraventricular nucleus; Microglia; Oxytocinergic and vasopressinergic neuron; P2X(7) receptor; Proinflammatory cytokines