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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| Atorvastatin | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | 1 tablet Unikalk 1 time pr day for 5 days |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Fractional excretion of sodium | Sodium excretion measured before, during and after L-NMMA infusion | 5 days treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Systolic blood pressure (SBP) | 5 days | |
| Pulse wave velocity | 5 days | |
| plasma renin concentration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Frank H Christensen, MD | Medicinsk Forskning | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medicinsk Forskning, Regionshospitalet Holstebro | Holstebro | 7500 | Denmark |
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| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D007674 | Kidney Diseases |
| ID | Term |
|---|---|
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Atorvastatin | Drug | Zarator, 80 mg pr day for 5 days |
|
|
| 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 |
| D052801 | Male Urogenital Diseases |
| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |