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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
26
1 tablet Unikalk 1 time pr day for 5 days
Zarator, 80 mg pr day for 5 days
Medicinsk Forskning, Regionshospitalet Holstebro
Holstebro, Denmark
Fractional excretion of sodium
Sodium excretion measured before, during and after L-NMMA infusion
Time frame: 5 days treatment
Systolic blood pressure (SBP)
Time frame: 5 days
Pulse wave velocity
Time frame: 5 days
plasma renin concentration
Time frame: 5 days
Augmentation index (AI)
Time frame: 5 days
Diastolic blood pressure
Time frame: 5 days
Plasma aldosterone concentration
Time frame: 5 days
Plasma and urinary albumin concentration
Time frame: 5 days
Urinary excretion of aquaporin-2
Time frame: 5 days
plasma atrial natriuretic peptide concentration
Time frame: 5 days
Plasma brain natriuretic peptide concentration
Time frame: 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)
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Time frame: 5 days