Aggravated renal inflammatory responses in TRPV1 gene knockout mice subjected to DOCA-salt hypertension.
To test the hypothesis that deletion of the transient receptor potential vanilloid type 1 (TRPV1) channel exaggerates hypertension-induced renal inflammatory response, wild-type (WT) or TRPV1-null mutant (TRPV1(-/-)) mice were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment for 4 wk. Mean arterial pressure (MAP) determined by radiotelemetry increased in DOCA-salt-treated WT or TRPV1(-/-) mice, whereas there was no difference in MAP between two strains at the baseline or after DOCA-salt treatment. DOCA-salt treatment increased urinary excretion of albumin and 8-isoprostane in both WT and TRPV1(-/-) mice, and the increases were greater in magnitude in the latter strain. Periodic acid-Schiff and Mason's trichrome staining showed that kidneys of DOCA-salt-treated TRPV1(-/-) mice exhibited more severe glomerulosclerosis and tubulointerstitial injury compared with DOCA-salt-treated WT mice. NF-kappaB assay showed that DOCA-salt treatment increased renal activated NF-kappaB concentrations in TRPV1(-/-) mice compared with WT mice. Immunostaining and ELISA assay revealed that DOCA-salt-treated TRPV1(-/-) mice had enhanced renal infiltration of monocyte/macrophage and lymphocyte, as well as increased renal levels of proinflammatory cytokine (TNF-alpha, IL-6) and chemokine (MCP-1) compared with DOCA-salt-treated WT mice. Renal ICAM-1 but not VCAM-1 expression was also greater in DOCA-salt-treated TRPV1(-/-) than WT mice. Dexamethasone (DEXA), an immunosuppressive drug, conveyed a renoprotective effect that was greater in DOCA-salt-treated TRPV1(-/-) compared with WT mice. These data show that renal inflammation is exacerbated in DOCA-salt hypertension when TRPV1 gene is deleted and that the deterioration is ameliorated by DEXA treatment, indicating that TRPV1 may act as a potential regulator of the inflammatory process to lessen renal injury in DOCA-salt hypertension.
Wang
Youping
Y
Department of Medicine, Michigan State University, East Lansing, MI 48824, USA.
Wang
Donna H
DH
D000818:Animals; D001794:Blood Pressure; D018932:Chemokine CCL2 / Q000378:metabolism; D003900:Desoxycorticosterone; D003907:Dexamethasone / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced* / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D017254:Leukemic Infiltration; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D009393:Nephritis / Q000209:etiology* / Q000473:pathology; D012720:Severity of Illness Index; D012965:Sodium Chloride; D050916:TRPV Cation Channels / Q000172:deficiency*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D016328:NF-kappa B; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D003907:Dexamethasone