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Randomized Controlled Trial
. 2018 Sep 21;19(1):244.
doi: 10.1186/s12882-018-1035-x.

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

Jeppe B Rosenbaek  1 , Erling B Pedersen  2 , Jesper N Bech  2
Affiliations
Randomized Controlled Trial

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

Jeppe B Rosenbaek et al. BMC Nephrol. .

Abstract

Background: Sodium nitrite (NaNO2) causes vasodilation, presumably by enzymatic conversion to nitric oxide (NO). Several enzymes with nitrite reducing capabilities have been discovered in vitro, but their relative importance in vivo has not been investigated. We aimed to examine the effects of NaNO2 on blood pressure, fractional sodium excretion (FENa), free water clearance (CH2O) and GFR, after pre-inhibition of xanthine oxidase, carbonic anhydrase, and angiotensin-converting enzyme. The latter as an approach to upregulate endothelial NO synthase activity.

Methods: In a double-blinded, placebo-controlled, crossover study, 16 healthy subjects were treated, in a randomized order, with placebo, allopurinol 150 mg twice daily (TD), enalapril 5 mg TD, or acetazolamide 250 mg TD. After 4 days of treatment and standardized diet, the subjects were examined at our lab. During intravenous infusion of 240 μg NaNO2/kg/hour for 2 h, we measured changes in brachial and central blood pressure (BP), plasma cyclic guanosine monophosphate (P-cGMP), plasma and urine osmolality, GFR by 51Cr-EDTA clearance, FENa and urinary excretion rate of cGMP (U-cGMP) and nitrite and nitrate (U-NOx). Subjects were supine and orally water-loaded throughout the examination day.

Results: Irrespective of pretreatment, we observed an increase in FENa, heart rate, U-NOx, and a decrease in CH2O and brachial systolic BP during NaNO2 infusion. P-cGMP and U-cGMP did not change during infusion. We observed a consistent trend towards a reduction in central systolic BP, which was only significant after allopurinol.

Conclusion: This study showed a robust BP lowering, natriuretic and anti-aquaretic effect of intravenous NaNO2 regardless of preceding enzyme inhibition. None of the three enzyme inhibitors used convincingly modified the pharmacological effects of NaNO2. The steady cGMP indicates little or no conversion of nitrite to NO. Thus the effect of NaNO2 may not be mediated by NO generation.

Trial registration: EU Clinical Trials Register, 2013-003404-39 . Registered December 3 2013.

Keywords: Aquaresis; Central blood pressure; Enzyme inhibition; Natriuresis; Sodium nitrite.

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Conflict of interest statement

Ethics approval and consent to participate

The study was approved by The Central Denmark Region Committees on Health Research Ethics, reference number 1-10-72-313-13 and the Danish Health and Medicines Authority, reference number 2013100160. The study was performed in accordance with the Declaration of Helsinki 2013. All subjects provided written informed consent. The experimental part of the study took place from November 28, 2014, to November 12, 2015. The trial was prospectively registered in The EU Clinical Trials Register, EudraCT 2013-003404-39.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Subject flow in the study and reasons for exclusion
See this image and copyright information in PMC

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