Role of TRPV1 channels in renal haemodynamics and function in Dahl salt-sensitive hypertensive rats

Abstract

This study tests the hypothesis that dysfunction of transient receptor potential vanilloid type 1 (TRPV1) channels occurs and contributes to the decrease in the glomerular filtration rate (GFR) and sodium/water excretion in Dahl salt-sensitive hypertensive rats.RecirculatingKrebs- Henseleit buffer addedwith inulin was perfused at a constant flowin the isolated kidneys of Dahl salt-sensitive (DS) or Dahl salt-resistant (DR) rats fed a high-salt (HS) or low-salt (LS) diet for 3 weeks.Perfusionpressures(PP)werepre-adjustedtothree levels (~100, ~150or~190 mmHg) with or without phenylephrine. Capsaicin, a selective TRPV1 agonist, in the presence or absence of capsazepine, a selective TRPV1 antagonist, was perfused. Basal GFR, urine flow rate (UFR) and Na+ excretion (UNaV) were significantly lower in DS-HS than in DR-HS, DS-LS and DRLS rats. Capsaicin caused pressure-dependent decreases in PP and increases in GFR, UFR and UNaV in all groups, with less magnitude of decreases in PP and increases in GFR, UFR andUNaV in DS-HS than in DR-HS, DS-LS and DR-LS rats. Capsazepine completely blocked the effect of capsaicin on PP, GFR, UFR and UNaV in all groups. Thus, these results show that TRPV1 function is impaired in the kidney of DS rats fed a high-salt diet, which may contribute to the decrease in GFR and renal excretory function in DS rats in the face of salt challenge. © 2008 The Authors. Journal compilation © 2008 The Physiological Society.