Table 4.

Effect of tolvaptan at baseline and during inhibition of the nitric oxide system on plasma concentrations of renin(PRC), angiotensin II (P-AngII), aldosterone (P-aldo) and vasopressin (P-AVP) in a randomized, placebo-controlled, double-blind, crossover study of 19 healthy subjects

Periods	Baseline	L-NMMA	Post infusion	P (GLM-within)
	11:00 AM	12:00 AM	1:00 PM
PRC(pg/ml)
Placebo	8.1 ± 4.3	6.1 ± 3.2**	5.9 ± 3.2**	0.670
Tolvaptan	9.9 ± 6.8	7.5 ± 4.6**	7.5 ± 5.4**
p (GLM between) 0.305
p (paired t-test, between)	0.101	0.050	0.038
P-AngII (pg/ml)
Placebo	9.5 ± 4	8.6 ± 3.7	8.0 ± 3.3*	0.156
Tolvaptan	11.9 ± 6.2	9.4 ± 4.6*	9.5 ± 5.1*
p (GLM between) 0.686
p (paired t-test, between)	0.094	0.403	0.117
P- Aldo (pmol/L)
Placebo	70 ± 2	75 ± 2	64 ± 2	0.949
Tolvaptan	71 ± 2	78 ± 2	66 ± 1
p (GLM between) 0.899
p (paired t-test, between)	0.962	0.785	0.840
P- AVP (pg/ml)
Placebo	0.20 ± 0.15	0.20 ± 0.15	0.20 ± 0.20
Tolvaptan	0.70 ± 0.45	0.70 ± 0.55	0.70 ± 0.60
p (Wilcoxon’s signed rank test, between)	<0.001	<0.001	<0.001

Data are shown as mean with ± SD or medians with ± interquartile range. General linear model (GLM) with repeated measures was performed for comparison within the group and intervention as between subject factor. Post-hoc Bonferoni test (*) was used for comparison of infusion period 90–150 min vs baseline and post infusion period 150–210 vs baseline. Paired t-test or Wilcoxon signed rank test was used for comparison between treatment group at baseline vs during infusion period 90–150 minu, and at baseline vs post infusion period 150 – 210 min. ^*p < 0.05; ^**p < 0.001;^***p < 0.0001.