title: [Role of transient receptor potential vanilloid type 1 and C-C chemokine receptor 2 in renal injury induced by salt-sensitive hype].
abstract: OBJECTIVE
  To determine the effects of transient receptor potential vanilloid type 1 (TRPV1) channel ablation and a chemokine receptor 2 (CCR2) antagonist on salt-sensitive hypertension-induced renal injury.
  
  
  METHODS
  Wild-type (WT) and TRPV1-null mutant (TRPV1(-/-)) mice were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment for 4 weeks with or without a CCR2 antagonist, RS504393 (n=8 for all the 4 groups). Sham WT and TRPV1(-/-) mice (both n=7) underwent uninephrectomy without receiving DOCA and saline. Systolic blood pressure, urinary excretion of albumin, 8-isoprostane and creatinine clearance for 24 hours were assayed during the experimental period and at the end of the 4-week treatment. The morphological analysis was performed in renal histological sections, including glomerulosclerosis, tubulointerstitial injury, and monocyte/macrophage infiltration.
  
  
  RESULTS
  Compared to the corresponding control mice, DOCA-salt treatment in both WT and TRPV1(-/-) mice led to increased systolic blood pressure (SBP), enhanced urinary excretion of albumin and 8-isoprostane, decreased creatinine clearance, increased glomerulosclerosis and tubulointerstitial injury associated with enhanced monocyte/macrophage infiltration (all P<0.05), all of which were much more severe in TRPV1(-/-) mice compared to WT mice with the exception of blood pressure (all P<0.05). RS5043943 attenuated DOCA-salt-induced changes in renal function and morphology in WT and TRPV1(-/-) mice (all P<0.05). There was no difference in blood pressure among DOCA-salt WT and TRPV1(-/-) mice with or without RS505393 with the exception of sham WT and TRPV1(-/-) mice (all P>0.05).
  
  
  CONCLUSIONS
  CCR2 antagonist inhibits DOCA-salt-induced renal injury and monocyte/macrophage infiltration in WT and TRPV1(-/-) mice with the greater in the latter strain. Activation of TRPV1 attenuates salt-sensitive hypertension-induced renal injury possibly via inhibition of CCR2-induced monocyte/macrophage infiltration.
authors.affiliation: Central Laboratory and Division of Cardiology,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000,China; Internal Medicine of Traditional Chinese Medicine,Henan University of Traditional Chinese Medicine,Zhengzhou 450008,China.
authors.forename: Fei-yun
authors.initials: FY
authors.lastname: Zhu
authors.affiliation: Central Laboratory and Division of Cardiology,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000.
authors.forename: Wei-hong
authors.initials: WH
authors.lastname: Liu
authors.affiliation: Central Laboratory and Division of Cardiology,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000.
authors.forename: Xiao-xiao
authors.initials: XX
authors.lastname: Wang
authors.affiliation: Central Laboratory and Division of Cardiology,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000.
authors.forename: Lin
authors.initials: L
authors.lastname: Cui
authors.affiliation: Central Laboratory and Division of Cardiology,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000.
authors.forename: Si
authors.initials: S
authors.lastname: Shen
authors.affiliation: Central Laboratory and Division of Cardiology,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000.
authors.forename: Ming-jun
authors.initials: MJ
authors.lastname: Zhu
authors.affiliation: Central Laboratory and Division of Cardiology,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000.
authors.forename: You-ping
authors.initials: YP
authors.lastname: Wang
mesh_terms: D000818:Animals; D006973:Hypertension / Q000150:complications* / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D012965:Sodium Chloride / Q000009:adverse effects; D050916:TRPV Cation Channels / Q000502:physiology*
chemical_list: C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D012965:Sodium Chloride