Received January 9, 2008
Revised February 8, 2008
Accepted after revision April 7, 2008
Cardiovascular Control [210]
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Role of TRPV1 in renal hemodynamics and function in Dahl salt-sensitive hypertensive rats
Jianping Li 1
Donna H. Wang 1*
1 Michigan State University
* To whom correspondence should be addressed. E-mail: donna.wang{at}ht.msu.edu.
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Abstract |
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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. Recirculating Krebs-Henseleit buffer added with inulin was perfused at a constant flow in 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 three weeks. Perfusion pressures (PP) were pre-adjusted to three levels (~100, ~150, ~190 mmHg) with or without phenylephrine. Capsaicin (Cap), a selective TRPV1 agonist, in the presence or absence of capsazepine (Capz), 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 DR-LS rats. Cap 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 and UNaV in DS-HS than in DR-HS, DS-LS and DR-LS rats. Capz fully blocked the effect of Cap 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 face of salt challenge.
Key Words:
Capsaicin, Hypertension, Sensory neurone