Table 4.

Effect of intravenous NaNO₂ on renal sodium and water regulation

	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

Effect of intravenous NaNO₂ on fractional excretion of sodium (FE_Na), GFR, free water clearance (C_H2O), 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

^* p < .05 within group vs. baseline (Bonferroni), ^† p < .05 vs. placebo at baseline