BackgroundSodium 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.MethodsIn 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.ResultsIrrespective 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.ConclusionThis 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 registrationEU Clinical Trials Register, 2013-003404-39. Registered December 3 2013.

BackgroundTolvaptan is a selective vasopressin receptor antagonist. Nitric Oxide (NO) promotes renal water and sodium excretion, but the effect is unknown in the nephron’s principal cells. In a dose-response study, we measured the effect of tolvaptan on renal handling of water and sodium and systemic hemodynamics, during baseline and NO-inhibition with L-NMMA (L-NG-monomethyl-arginine).MethodsIn a randomized, placebo-controlled, double blind, cross over study, 15 healthy subjects received tolvaptan 15, 30 and 45 mg or placebo. L-NMMA was given as a bolus followed by continuous infusion during 60 min. We measured urine output (UO), free water clearance (CH2O), fractional excretion of sodium (FENa), urinary aquaporin-2 channels (u-AQP2) and epithelial sodium channels (u-ENaCγ), plasma vasopressin (p-AVP) and central blood pressure (cBP).ResultsDuring baseline, FENa was unchanged. Tolvaptan decreased u-ENaCγ dose-dependently and increased p-AVP threefold, whereas u-AQP2 was unchanged. During tolvaptan with NO-inhibition, UO and CH2O decreased dose-dependently. FENa decreased dose-independently and u-ENaCγ remained unchanged. Central BP increased equally after all treatments.ConclusionsDuring baseline, fractional excretion of sodium was unchanged. During tolvaptan with NO-inhibition, renal water excretion was reduced dose dependently, and renal sodium excretion was reduced unrelated to the dose, partly via an AVP dependent mechanism. Thus, tolvaptan antagonized the reduction in renal water and sodium excretion during NO-inhibition. Most likely, the lack of decrease in AQP2 excretion by tolvaptan could be attributed to a counteracting effect of the high level of p-AVP.Trial registrationClinical Trial no: NCT02078973. Registered 1 March 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-017-0501-1) contains supplementary material, which is available to authorized users.

Correct measurement of blood pressure (BP) is important for optimal diagnosis and treatment of patients with hypertension. The aim of this study was to compare a wrist-worn device using tonometric measurements of BP to a conventional device using oscillometric measurements of 24 h BP, diagnosing of hypertension, and non-dipping. Methods: One-hundred patients in the Renal Outpatient Clinic had 24 h ambulatory BP monitoring performed with a tonometric device, BPro, and an oscillometric device, A&D, simultaneously. Results: Twenty-four-hour and daytime systolic BP was significantly lower using tonometric monitoring compared to oscillometric (7 and 6 mmHg, respectively, p< 0.001). In the population of patients diagnosed with hypertension, the tonometric device diagnosed 90% of patients with uncontrolled hypertension correctly (positive predictive value), whereas 49% of patients classified as normotensive were uncontrolled hypertensive (negative predictive value). The mean difference between relative nocturnal BP decrease between tonometric and oscillometric was 2±8% (p< 0.01), and 33% of patients classified as dippers were nondippers (negative predictive value). Conclusion: Using the BPro device for tonometric monitoring of BP and classification of hypertension and non-dipping in patients diagnosed with hypertension leads to misclassification of patients. Therefore, the BPro device is not suitable for clinical practice in hypertensive patients from a Renal Outpatient Clinic.