The effect of sodium nitrite infusion on renal variables, brachial and central blood pressure during enzyme inhibition by allopurinol, enalapril or acetazolamid in healthy subjects. A randomized, double-blinded, placebo controlled, cross-over study

INTERVENTION: Trade Name: Allopurinol Pharmaceutical Form: Tablet INN or Proposed INN: ALLOPURINOL CAS Number: 315‐30‐0 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: Enalapril Pharmaceutical Form: Tablet INN or Proposed INN: ENALAPRIL Other descriptive name: ENALAPRIL MALEATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: Acetazolamid Pharmaceutical Form: Tablet INN or Proposed INN: ACETAZOLAMIDE CAS Number: 59‐66‐5 Other descriptive name: ACETAZOLAMIDE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: The normal physiological responses in healthy subjects ; MedDRA version: 14.1 Level: SOC Classification code 10022891 Term: Investigations System Organ Class: 10022891 ‐ Investigations Therapeutic area: Body processes [G] ‐ Circulatory and Respiratory Physiological Phenomena [G09] PRIMARY OUTCOME: Main Objective: To investigate how inhibition of xanthine oxidase, angiotensine converting enzyme and carbonic anhydrase affects the response to sodium nitrite infusion in healthy subjects Primary end point(s): Fractional sodium excretion (FENa) Secondary Objective: Not applicable Timepoint(s) of evaluation of this end point: Subjects will be followed with repeated blood samples for the duration of the examination day, from 8 AM to 2 PM. SECONDARY OUTCOME: Secondary end point(s): Brachial blood pressure and central aortic systolic blood pressure Glomerular filtration rate; Absolute sodium excretion and proximal tubular sodium transport (lithium clearance); Plasma levels of renin, angiotensin 2, aldosteron, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cGMP, endothelin and vasopressin; Urinary excretion of aquaporin 2, ENaC, c‐AMP, NKCC2 ; Renal clearance of nitrate and nitrite; Free water clearance Timepoint(s) of evaluation of this end point: Subjects will be followed with repeated measurements, blood and urine samples for the duration of the examination day, from 8 AM to 2 PM. INCLUSION CRITERIA: Age 18‐40 years, BMI 18,5‐30, women must use contraception Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range