Effect of vasopressin antagonism on renal handling of sodium and water and central and brachial blood pressure during inhibition of the nitric oxide system in healthy subjects

BMC Nephrology

Erling Bjerregaard Pedersen¹  Jesper Nørgaard Bech¹  Janni Majgaard Jensen¹  Frank Holden Mose¹  Safa Al Therwani¹ 

[1]University Clinic in Nephrology and Hypertension, Department of Medical Research, Holstebro Hospital and Aarhus University, Hospital Unit Jutland West, Laegaardvej 12, 7500 Holstebro, Denmark

关键词: Angiotensin II;    Renin;    AVP;    Blood pressure;    ENaC;    AQP2;    Nitric oxide;    Tolvaptan;   

Others  :  797851
DOI  :  10.1186/1471-2369-15-100

 received in 2014-01-22, accepted in 2014-06-19,  发布年份 2014

【 摘 要 】

Background

Tolvaptan is a selective vasopressin receptor antagonist (V2R) that increases free water excretion. We wanted to test the hypotheses that tolvaptan changes both renal handling of water and sodium and systemic hemodynamics during basal conditions and during nitric oxide (NO)-inhibition with L-NG-monomethyl-arginine (L-NMMA).

Methods

Nineteen healthy subjects were enrolled in a randomized, placebo-controlled, double-blind, crossover study of two examination days. Tolvaptan 15 mg or placebo was given in the morning. L-NMMA was given as a bolus followed by continuous infusion during 60 minutes. We measured urine output(UO), free water clearance (C_H2O), fractional excretion of sodium (FE_Na), urinary aquaporin-2 channels (u-AQP2) and epithelial sodium channels (u-ENaC_γ), plasma vasopressin (p-AVP), central and brachial blood pressure(cBP, bBP).

Results

During baseline conditions, tolvaptan caused a significant increase in UO, C_H2O and p-AVP, and FE_Na was unchanged. During L-NMMA infusion, UO and C_H2O decreased more pronounced after tolvaptan than after placebo (-54 vs.-42% and -34 vs.-9% respectively). U-AQP2 decreased during both treatments, whereas u-ENaC_γ decreased after placebo and increased after tolvaptan. CBP and bBP were unchanged.

Conclusion

During baseline conditions, tolvaptan increased renal water excretion. During NO-inhibition, the more pronounced reduction in renal water excretion after tolvaptan indicates that NO promotes water excretion in the principal cells, at least partly, via an AVP-dependent mechanism. The lack of decrease in u-AQP2 by tolvaptan could be explained by a counteracting effect of increased plasma vasopressin. The antagonizing effect of NO-inhibition on u-ENaC suggests that NO interferes with the transport via ENaC by an AVP-dependent mechanism.

【 授权许可】

   
2014 Al Therwani et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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