title: TRPV1 ablation aggravates inflammatory responses and organ damage during endotoxic shock.
abstract: To test the hypothesis that ablation of transient receptor potential vanilloid type 1 (TRPV1) channels leads to exacerbated inflammatory responses and organ damage during endotoxic shock, lipopolysaccharide (LPS; 5 million endotoxin units/kg of body weight) was injected intraperitoneally (i.p.) into wild-type (WT) and TRPV1-null mutant (TRPV1(-/-)) mice. Mean arterial pressure and heart rate, determined by radiotelemetry, were severely depressed after LPS injection into WT and TRPV1(-/-) mice, with no distinction between the two strains. At 24 h after LPS injection, renal glomerular hypercellularity and hepatocellular injury were observed in both strains, accompanying further elevated serum levels of creatinine and alanine aminotransferase in TRPV1(-/-) mice compared to those in WT mice. At 6 or 24 h after LPS injection, neutrophil recruitment into kidneys and livers, serum cytokine (tumor necrosis factor alpha [TNF-α], interleukin 1β [IL-1β], IL-6) and renal chemokine (KC, macrophage inflammatory protein 2 [MIP-2]) levels, and renal VCAM-1 and ICAM-1 expression were greater in TRPV1(-/-) mice than WT mice. In addition, increased plasma calcitonin gene-related peptide (CGRP) levels observed in WT mice 6 h after LPS injection were absent in TRPV1(-/-) mice. Thus, TRPV1 ablation aggravates inflammatory responses, including neutrophil infiltration, proinflammatory cytokine production, and adhesion molecule expression, leading to intensified organ damage during endotoxic shock in the absence of worsened circulatory failure. The data indicate that TRPV1 activation may attenuate endotoxin-induced organ damage, possibly via its anti-inflammatory action rather than alteration of hemodynamics.
authors: Central Laboratory and Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine, Zhengzhou, China.
authors: Youping
authors: Y
authors: Wang
authors: Donna H
authors: DH
authors: Wang
mesh_terms: D000818:Animals; D006505:Hepatitis / Q000473:pathology; D006651:Histocytochemistry; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D009393:Nephritis / Q000473:pathology; D012772:Shock, Septic / Q000473:pathology*; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse
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