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Table 4 Effect of intravenous NaNO2 on renal sodium and water regulation

From: The effect of sodium nitrite infusion on renal function, brachial and central blood pressure during enzyme inhibition by allopurinol, enalapril or acetazolamide in healthy subjects: a randomized, double-blinded, placebo-controlled, crossover study

 

Baseline

Infusion

Post-infusion

p Friedman/RM ANOVA (one-way)

30 min

60 min

90 min

120 min

150 min

180 min

FENa (%)

 Placebo

1.26 [1.05;1.47]

1.26 [1.09;1.43]

1.43 [1.25;1.62]

1.38 [1.24;1.52]

1.57 [1.36;1.78]

1.53 [1.34;1.73]

1.41 [1.26;1.56]

.001

 Allopurinol

1.36 [0.96;1.75]

1.41 [1.05;1.76]

1.52 [1.20;1.83]

1.53 [1.22;1.83]

1.66 [1.32;2.00]*

1.69 [1.40;1.98]*

1.59 [1.33;1.85]

.002

 Enalapril

1.15 [0.84;1.46]

1.30 [1.01;1.60]

1.42 [1.15;1.68]*

1.45 [1.20;1.71]*

1.59 [1.34;1.83]*

1.56 [1.32;1.81]*

1.52 [1.29;1.74]*

<.001

 Acetazolamide

1.08 [0.86;1.29]

1.25 [1.01;1.49]

1.35 [1.08;1.63]

1.29 [1.07;1.51]

1.42 [1.15;1.69]*

1.44 [1.17;1.71]*

1.28 [1.05;1.52]

.001

 pinteraction (pretreatment x time)

.535

   

GFR (ml/min/1.73 m2)

 Placebo

98 [90;105]

104 [96;111]

98 [91;105]

105 [97;113]*

101 [92;110]

99 [93;106]

100 [91;109]

.027

 Allopurinol

99 [90;108]

102 [93;112]

97 [89;105]

103 [94;112]

98 [88;108]

99 [91;107]

102 [92;111]

.132

 Enalapril

101 [92;110]

104 [94;114]

101 [94;108]

104 [96;112]

100 [91;109]

102 [94;109]

102 [94;110]

.568

 Acetazolamide

83 [76;89]†

84 [77;92]

77 [70;83]*

83 [75;91]

83 [76;89]

83 [76;89]

85 [78;92]

.012

 pinteraction (pretreatment x time)

.494

   

CH20 (ml/min)

 Placebo

4.58 [3.66;5.50]

2.87 [2.08;3.65]

1.87 [1.36;2.38]*

2.27 [1.46;3.08]*

2.85 [2.11;3.59]

2.64 [2.00;3.28]*

2.85 [2.15;3.55]*

<.001

 Allopurinol

4.56 [3.64;5.48]

3.05 [2.02;4.07]

2.54 [1.82;3.27]*

2.04 [0.98;3.10]*

3.00 [2.11;3.90]

3.06 [2.19;3.93]

3.26 [2.40;4.12]

.011

 Enalapril

4.82 [3.70;5.94]

3.57 [2.48;4.65]

2.28 [1.26;3.29]*

2.28 [1.48;3.08]*

3.24 [2.59;3.89]

2.23 [1.26;3.21]*

2.67 [1.71;3.63]

.001

 Acetazolamide

3.91 [2.80;5.01]

1.99 [1.12;2.87]

1.69 [0.93;2.46]

1.63 [0.87;2.39]*

2.60 [1.78;3.42]

2.67 [1.78;3.55]

2.60 [1.80;3.40]

.004

 pinteraction (pretreatment x time)

.682

   

P-AVP (pg/ml)

 Placebo

0.32 [0.25;0.38]

 

0.25 [0.20;0.30]*

 

0.27 [0.21;0.33]*

  

.012

 Allopurinol

0.29 [0.21;0.36]

 

0.28 [0.22;0.33]

 

0.25 [0.21;0.29]

  

.414

 Enalapril

0.26 [0.20;0.33]

 

0.21 [0.17;0.26]

 

0.23 [0.18;0.28]

  

.213

 Acetazolamide

0.29 [0.22;0.36]

 

0.27 [0.19;0.35]

 

0.28 [0.22;0.34]

  

.770

 pinteraction (pretreatment x time)

.630

   

U-AQP2 (ng/min)

 Placebo

1.26 [1.12;1.41]

1.25 [1.06;1.45]

1.23 [1.10;1.35]

1.18 [1.04;1.33]

1.23 [1.08;1.39]

1.19 [1.06;1.33]

1.13 [1.02;1.23]

.167

 Allopurinol

1.45 [1.27;1.63]†

1.37 [1.26;1.48]

1.31 [1.20;1.42]

1.34 [1.21;1.47]

1.33 [1.13;1.54]

1.31 [1.20;1.42]

1.28 [1.17;1.39]

.080

 Enalapril

1.29 [1.13;1.44]

1.23 [1.09;1.37]

1.28 [1.14;1.42]

1.26 [1.13;1.40]

1.28 [1.09;1.46]

1.33 [1.18;1.48]

1.18 [1.06;1.31]

.131

 Acetazolamide

1.30 [1.15;1.45]

1.26 [1.08;1.44]

1.21 [1.07;1.36]

1.19 [1.04;1.35]

1.25 [1.09;1.41]

1.26 [1.08;1.43]

1.21 [1.06;1.37]

.363

 pinteraction (pretreatment x time)

.590

   

U-ENaCγ (ng/min)

 Placebo

0.44 (0.38;0.51)

0.44 (0.33;0.51)

0.47 (0.35;0.54)

0.45 (0.36;0.59)

0.40 (0.36;0.57)

0.43 (0.36;0.56)

0.43 (0.32;0.46)

.331

 Allopurinol

0.43 (0.40;0.65)

0.42 (0.38;0.54)

0.39 (0.34;0.54)

0.47 (0.42;0.61)

0.43 (0.30;0.54)*

0.42 (0.35;0.51)

0.39 (0.34;0.50)

.020

 Enalapril

0.44 (0.40;0.64)

0.40 (0.35;0.49)

0.39 (0.34;0.60)

0.45 (0.31;0.53)

0.39 (0.36;0.55)

0.41 (0.33;0.57)

0.45 (0.40;0.53)

.215

 Acetazolamide

0.68 (0.48;0.95)†

0.57 (0.42;1.01)

0.59 (0.45;0.94)

0.53 (0.48;0.88)

0.55 (0.45;0.93)

0.71 (0.53;0.94)

0.64 (0.49;0.89)

.561

  1. Effect of intravenous NaNO2 on fractional excretion of sodium (FENa), GFR, free water clearance (CH2O), urinary excretion rates of aquaporin-2 (AQP2) and γ-subunit of the epithelial sodium channel (ENaCγ) in 14 healthy subjects and arginine vasopressine (AVP) in 16 healthy subjects after 4 days pretreatment with allopurinol, enalapril, acetazolamide, or placebo. Normal distributed data are presented as means with 95% confidence interval in brackets and non-parametric data as medians with 25th and 75th percentiles in parentheses. Statistics were performed using one-way repeated measures (RM) ANOVA for comparing over time and two-way RM ANOVA with time and pretreatment as within factors to test for interaction. Pairwise comparison where performed using Student’s t-test. U-ENaCγ were tested using Friedman test for comparing over time and Wilcoxon’s signed rank test for pairwise comparison with placebo or baseline
  2. * p < .05 within group vs. baseline (Bonferroni), † p < .05 vs. placebo at baseline