Deletion of transient receptor potential vanilloid type 1 receptors exaggerates renal damage in deoxycorticosterone acetate-salt hypertension.
To determine whether the transient receptor potential vanilloid type 1 (TRPV1) channel provides protection against hypertension-induced renal damage, hypertension was induced by uninephrectomy and by giving deoxycorticosterone acetate (DOCA)-salt in wild-type (WT) and TRPV1-null mutant (TRPV1-/-) mice. Mean arterial pressure, as determined by radiotelemetry, increased significantly and reached the peak 7 days after DOCA-salt treatment in both WT and TRPV1-/- mice. There was no difference in mean arterial pressure between the 2 strains at the baseline or at the peak that lasted for 4 treatment weeks. DOCA-salt treatment in both WT and TRPV1-/- mice led to increased urinary excretion of albumin and 8-isoprostane, glomerulosclerosis, renal cortical tubulointerstitial injury, tubulointerstitial fibrosis, increased number of tubular proliferating cell nuclear antigen-positive cells, and renal monocyte/macrophage infiltration, all of which were much more severe in DOCA-salt-treated TRPV1-/- compared with DOCA-salt-treated WT mice. Renal TRPV1 protein expression, but not the renal anandamide content, was elevated in DOCA-salt-treated WT compared with vehicle-treated WT mice. Renal anandamide levels were markedly elevated in DOCA-salt-treated TRPV1-/- but not in vehicle-treated TRPV1-/- mice. Thus, our data show that ablation of the TRPV1 gene exacerbates renal damage induced by DOCA-salt hypertension, indicating that TRPV1 may constitute a protective mechanism against end-organ damage induced by hypertension.
Wang
Youping
Y
Department of Medicine, Michigan State University, East Lansing, MI 48824, USA.
Babánková
Dagmar
D
Huang
Jie
J
Swain
Greg M
GM
Wang
Donna H
DH
D000419:Albuminuria / Q000175:diagnosis / Q000209:etiology; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate; D006973:Hypertension / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology*; D007150:Immunohistochemistry; D028421:Isoprostanes / Q000652:urine; D051379:Mice; D008817:Mice, Mutant Strains; D009400:Nephrosclerosis / Q000209:etiology* / Q000473:pathology*; D011336:Probability; D011897:Random Allocation; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D016482:Urinalysis
D028421:Isoprostanes; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C494484:TRPV1 receptor; D003900:Desoxycorticosterone