The Effects of Atorvastatin on the Nitric Oxide-system in Healthy Young Man
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Fractional excretion of sodium
Study Overview
Brief Summary
It has been documented that statin reduce mortality and morbidity in patients with cardiovascular disease. This effect can partly be related to a reduction in cholesterol levels in blood. Nitric oxide (NO) production is reduced in several chronic diseases such as nephropathy, diabetes and hypertension. The purpose of this study is to investigate the effect of Atorvastatin treatment on the NO-system measuring renal and cardiovascular variables in healthy man.
Detailed Description
Subjects will be examined on two examination days. 4 days prior to each examination day subjects are treated with either atorvastatin or placebo. During treatment periods subject are given a standardized diet.
On the examination days subject are given L-NMMA(L-NG-monomethyl Arginine citrate), a NO inhibitor, 6 mg bolus infusion followed by continuous 4 mg/kg/hr infusion for 1 hour. Renal function, central hemodynamic and vasoactive hormones are evaluated prior, during and after L-NMMA infusion.
Renal function is measured by renal clearance of 51Cr-EDTA and urinary sodium, potassium and albumin concentration. Urinary excretion of protein from sodium channels such as the NaCl cotransporter (NCC), the Na-K-Cl cotransporter (NKCC) and the epithelial sodium channel (ENaC)will be measured to evaluate channel activity in the nephron.
Central blood pressure, pulse wave analysis, and augmentation index are measured using SphygmoCor® from Atcor.
The vasoactive hormones aldosterone, renin, angiotensin II, atrial natriuretic peptide (ANP), brain natriuretic (BNP) and endothelin is measured in plasma
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 40 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Men and women, age 18-40 years
- •Body Mass Index (BMI) 18,5-30 kg/m2
Exclusion Criteria
- •Arterial hypertension (>140 mmHg systolic and/or 90 mmHg diastolic)
- •Anamnestic or clinical signs of heart, lung, lever, kidney and brain disease
- •Neoplastic disease
- •Alcohol abuse,
- •Drug abuse
- •Medical treatment except oral anticontraceptive
- •Pregnancy or
- •Abnormal blood and urine sample
- •Abnormal ECG
- •Blood donation within a month before examination
Arms & Interventions
Placebo
Intervention: Placebo (Drug)
Atorvastatin
Intervention: Atorvastatin (Drug)
Outcomes
Primary Outcomes
Fractional excretion of sodium
Time Frame: 5 days treatment
Sodium excretion measured before, during and after L-NMMA infusion
Secondary Outcomes
- Systolic blood pressure (SBP)(5 days)
- Pulse wave velocity(5 days)
- plasma renin concentration(5 days)
- Augmentation index (AI)(5 days)
- Diastolic blood pressure(5 days)
- Plasma aldosterone concentration(5 days)
- Plasma and urinary albumin concentration(5 days)
- Urinary excretion of aquaporin-2(5 days)
- plasma atrial natriuretic peptide concentration(5 days)
- Plasma brain natriuretic peptide concentration(5 days)
- Urinary excretion of protein from sodium channels such as the NaCl cotransporter (NCC), the Na-K-Cl cotransporter (NKCC) and the epithelial sodium channel (ENaC)(5 days)