title: Hemodynamic changes during hemodialysis: role of nitric oxide and endothelin.
abstract: BACKGROUND
  Etiology of dialysis induced hypotension and hypertension remains speculative. There is mounting evidence that nitric oxide (NO) and endothelin (ET-1) may play a vital role in these hemodynamic changes. We examined the intradialytic dynamic changes in NO and ET-1 levels and their role in the pathogenesis of hypotension and rebound hypertension during hemodialysis (HD).
  
  
  METHODS
  The serum nitrate + nitrite (NT), fractional exhaled NO concentration (FENO), L-arginine (L-Arg), NGNG-dimethyl-L-arginine (ADMA) and endothelin (ET-1) profiles were studied in 27 end-stage renal disease (ESRD) patients on HD and 6 matched controls. The ESRD patients were grouped according to their hemodynamic profile; Group I patients had stable BP throughout HD, Group II had dialysis-induced hypotension, and Group III had intradialytic rebound hypertension.
  
  
  RESULTS
  Pre-dialysis FENO was significantly lower in the dialysis patients compared to controls (19.3 +/- 6.3 vs. 28.6 +/- 3.4 ppb, P < 0.002). Between the experimental groups, pre-dialysis FENO was significantly higher in Group II (24.1 +/- 6.7 ppb) compared to Group I (17.8 +/- 5.6 ppb) and Group III (16.1 +/- 4.2 ppb; P < 0.05). Post-dialysis, FENO increased significantly from the pre-dialysis values (19.3 +/- 6.3 vs. 22.6 +/- 7.9 ppb; P=0.001). Pre-dialysis NT (34.4 +/- 28.2 micromol/L/L) level was not significantly different from that of controls (30.2 +/- 12.3 micromol/L/L). Serum NT decreased from 34.4 +/- 28.2 micromol/L/L at initiation of dialysis to 10.0 +/- 7.4 micormol/L/L at end of dialysis (P < 0.001). NT concentration was comparable in all the three groups at all time points. Pre-dialysis L-Arg (105.3 +/- 25.2 vs. 93.7 +/- 6.0 micromol/L/L; P < 0.05) and ADMA levels were significantly higher in ESRD patients (4.0 +/- 1.8 vs. 0.9 +/- 0.2 micromol/L/L; P < 0.001) compared to controls. Dialysis resulted in significant reduction in L-Arg (105.3 +/- 25.2 vs. 86.8 +/- 19.8 micromol/L/L; P < 0.005) and ADMA (4.0 +/- 1.8 vs. 1.6 +/- 0.7 micromol/L/L; P < 0.001) concentrations. Pre-dialysis ET-1 levels were significantly higher in ESRD patients compared to the controls (8.0 +/- 1.9 vs. 12.7 +/- 4.1 pg/mL; P < 0.002), but were comparable in the three study groups. Post-dialysis ET-1 levels did not change significantly in Group I compared to pre-dialysis values (14.3 +/- 4.3 vs.15.0 +/- 2.4 pg/mL, P=NS). However, while the ET-1 concentration decreased significantly in Group II (12.0 +/- 4.0 vs. 8.7 +/- 1.8 pg/mL, P < 0.05), it increased in Group III from pre-dialysis levels (12.8 +/- 3.8 vs. 16.7 +/- 4.5 pg/mL, P=0.06).
  
  
  CONCLUSIONS
  Pre-dialysis FENO is elevated in patients with dialysis-induced hypotension and may be a more reliable than NT as a marker for endogenous NO activity in dialysis patients. Altered NO/ET-1 balance may be involved in the pathogenesis of rebound hypertension and hypotension during dialysis.
authors.affiliation: Division of Nephrology, University of New Mexico, Albuquerque, New Mexico 87131-5271, USA. draj@salud.unm.edu
authors.forename: Dominic S C
authors.initials: DS
authors.lastname: Raj
authors.forename: Brad
authors.initials: B
authors.lastname: Vincent
authors.forename: Keith
authors.initials: K
authors.lastname: Simpson
authors.forename: Etsuro
authors.initials: E
authors.lastname: Sato
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Jones
authors.forename: Tomas C
authors.initials: TC
authors.lastname: Welbourne
authors.forename: Moshe
authors.initials: M
authors.lastname: Levi
authors.forename: Vallabh
authors.initials: V
authors.lastname: Shah
authors.forename: Pedro
authors.initials: P
authors.lastname: Blandon
authors.forename: Philip
authors.initials: P
authors.lastname: Zager
authors.forename: Richard A
authors.initials: RA
authors.lastname: Robbins
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006801:Humans; D006977:Hypertension, Renal / Q000209:etiology* / Q000378:metabolism; D007022:Hypotension / Q000209:etiology* / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D006435:Renal Dialysis / Q000009:adverse effects*
chemical_list: D019332:Endothelin-1; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine