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| Name | Class |
|---|---|
| NHS Lothian | OTHER_GOV |
| British Heart Foundation | OTHER |
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The apelin-APJ system is a relatively new discovery. It has generated interest in part due to it's apparent ability to counteract the renin-angiotensin system, which is frequently overactive in many cardiovascular disease.
Two of the main actions of apelin are to increase the pumping ability of the heart and cause blood vessels to relax. The investigators wish to assess if these actions are altered in the setting of normal renin-angiotensin activation and increased renin-angiotensin activity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sodium depletion | Experimental | Subjects will be randomised to normal diet or sodium depleted diet. The sodium depletion protocol comprises of a single oral dose of 40 mg of furosemide followed by an out-patient diet containing >2000 kcal of energy, >60 g of protein, <12 mmol of sodium and <70 mmol of potassium per day for 3 days prior to study. This diet is know to increase the activity of the renin-angiotensin system. |
|
| Normal diet | Placebo Comparator | Subjects will be randomised to a normal diet, with no restriction on sodium intake during the three days prior to the study. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Apelin | Drug | Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial apelin infusions at 0.3, 1.0 and 3.0 nanomol/ml. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in cardiac output | 12 months | |
| Change in apelin mediated vasodilatation | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in systemic haemodynamics | 12 months | |
| Change in relevant neurohumoral hormones | 12 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clincial Research Facility, Royal Infirmary of Edinburgh, 51 Little France Cresc | Edinburgh | EH16 4SA | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23519586 | Derived | Barnes GD, Alam S, Carter G, Pedersen CM, Lee KM, Hubbard TJ, Veitch S, Jeong H, White A, Cruden NL, Huson L, Japp AG, Newby DE. Sustained cardiovascular actions of APJ agonism during renin-angiotensin system activation and in patients with heart failure. Circ Heart Fail. 2013 May;6(3):482-91. doi: 10.1161/CIRCHEARTFAILURE.111.000077. Epub 2013 Mar 21. |
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| Acetylcholine | Drug | Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 5, 10 and 20 microg/min |
|
| Sodium nitroprusside | Drug | Using the technique of venous occlusive plethysmography subjects will receive three intrabrachial acetylcholine infusions at 1, 2 and 4 microg/min |
|
| Systemic apelin infusion | Drug | Following plethysmography patients will receive systemic infusion of (Pry)Apelin-13 (30, 100 and 300 nmol/min) for 5 mins cardiac output, blood pressure, heart rate and systemic vascular resistance will be measured at 5-min intervals. |
|
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D006333 | Heart Failure |
| D000783 | Aneurysm |
| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D000073861 | Apelin |
| D000109 | Acetylcholine |
| D009599 | Nitroprusside |
| ID | Term |
|---|---|
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001685 | Biological Factors |
| D001679 | Biogenic Amines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D005292 | Ferricyanides |
| D003486 | Cyanides |
| D000838 | Anions |
| D007477 | Ions |
| D004573 | Electrolytes |
| D007287 | Inorganic Chemicals |
| D005290 | Ferric Compounds |
| D058085 | Iron Compounds |
| D006856 | Hydrogen Cyanide |
| D017672 | Nitrogen Compounds |
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