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 TRPV10(-/-) compared with DOCA- salttreated 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.