Abstract 8938: Heightened Renal Sympathetic Nerve Activity in Response to High Salt Intake After Renal Ischemia-Reperfusion Injury: Role Of TRPV1

Abstract

Increased salt sensitivity occurs following ischemia-reperfusion (I/R) injury of the kidney. We test the hypothesis that renal sympathetic nerve activity is increased in response to high salt (HS) intake after I/R of the kidney, which can be prevented by activation of the transient receptor potential vanilloid type 1 (TRPV1) prior to renal I/R. Rats were fed a 0.4 % NaCl diet for 5 wks after I/R, following by a 4 % NaCl diet for 4 more wks in four groups: Sham, I/R, I/R+high dose capsaicin (HDC), and I/R+low dose capsaicin (LDC). TRPV1 was activated or down-regulated by s.c. injection of a low (1 mg/kg) or high (100 mg/kg) dose of capsaicin, respectively, 3 hrs before I/R. Renal TRPV1 protein expression was decreased after I/R and further reduced in I/R+HDC but unchanged in I/R+LDC compared to Sham (Sham: 0.44±0.04 vs I/R: 0.26±0.02 vs I/R+HDC: 0.17±0.01 vs I/R+LDC: 0.38±0.05, p<0.05). Systolic blood pressure and renal excretory function were not different among four groups 5 wks after I/R, but gradually elevated or deteriorated, respectively, when switched to HS for the remaining 4 wks in I/R and I/R+HDC but not I/R+LDC, with greater intensity in I/R+HDC ( p<0.05). At the end of HS treatment, afferent renal nerve activity in response to unilateral intra-pelvis administration of capsaicin was decreased in I/R and further suppressed in I/R+HDC but unchanged in I/R+LDC (Sham: 123±7 vs I/R: 81±9 vs I/R+HDC: 37±6 vs I/R+LDC: 120±13%, p<0.05). Efferent renal nerve activity in response to intrathecal administration of muscimol (3 nmol/kg), a selective activator of GABA-A receptors, was decreased in I/R and further suppressed in I/R+HDC but unchanged in I/R+LDC (Sham: -21±1 vs I/R: -42±3 vs I/R+HDC: -53±2 vs I/R+LDC: -25±4%, p<0.05). Urinary norepinephrine levels were increased in I/R and further elevated in I/R+HDC but unchanged in I/R+LDC (Sham: 785±98 vs I/R: 1311±98 vs I/R+HDC: 1731±140 vs I/R+LDC: 1018±85 ng/day, p<0.05). These data show that renal sympathetic drive is increased in response to HS intake after I/R, which can be prevented by TRPV1 activation prior to renal I/R, indicating that TRPV1 may prevent increased salt sensitivity after I/R via suppression of heightened renal sympathetic nerve activity.