Interaction of Apelin and Angiotensin in the Human Forearm Circulation

Study Overview
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Brief Summary
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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. Angiotensin has a powerful ability to cause blood vessels constrict and reduces their diameter. One of the actions of apelin is to cause blood vessels to relax and the investigators specifically wish test the hypothesis that apelin will cause blood vessels constricted by angiotensin II to relax.

Official Title
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Investigating the Interaction of Apelin and Angiotensin II Peripheral Resistance Vessels in Vivo in Man

Conditions
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Heart Disease, Vasodilation

Intervention / Treatment
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* Drug: Apelin infusion
* Drug: Sodium nitroprusside infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 18 years old Exclusion Criteria: Lack of informed consent Age < 18 years, Current involvement in other research studies, Systolic blood pressure >190 mmHg or <100 mmHg Malignant arrhythmias Renal or hepatic failure Haemodynamically significant aortic stenosis Severe or significant co morbidity Women of childbearing potential. Any regular medication Previous history of any cardiovascular disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Angiotensin II infusion<br>Using forearm venous occlusion plethysmography angiotensin II will be infused to cause reduction in forearm blood flow. Infusion of apelin and sodium nitroprusside will given and vasodilatation will be assessed. Blood samples for the infused arm and contra-lateral arm will be taken at regular time points to assess local and systemic changes in relevant hormones. | Drug: Apelin infusion<br>* Infusion of up to 10picmol/min will be administered intra-arterially to induce vasoconstriction. Thereafter infusions of apelin (0.1, 1.0, 3.0nmol/min) will be given for 6mins each. During the same study, sodium nitroprusside will given (1.0, 2.0, 4.0 microg/min) for 6mins.<br>Drug: Sodium nitroprusside infusion<br>* Infusion of up to 150-600picmol/min will be administered intra-arterially to induce vasoconstriction. Thereafter infusions of apelin (0.1, 1.0, 3.0nmol/min) will be given for 6mins each. During the same study, sodium nitroprusside will given (1.0, 2.0, 4.0 microg/min) for 6mins.<br>|
| Active Comparator: Noradrenaline<br>Using forearm venous occlusion plethysmography noradrenaline will be infused to cause reduction in forearm blood flow. Infusion of apelin and sodium nitroprusside will given and vasodilatation will be assessed. Blood samples for the infused arm and contra-lateral arm will be taken at regular time points to assess local and systemic changes in relevant hormones. | Drug: Apelin infusion<br>* Infusion of up to 10picmol/min will be administered intra-arterially to induce vasoconstriction. Thereafter infusions of apelin (0.1, 1.0, 3.0nmol/min) will be given for 6mins each. During the same study, sodium nitroprusside will given (1.0, 2.0, 4.0 microg/min) for 6mins.<br>Drug: Sodium nitroprusside infusion<br>* Infusion of up to 150-600picmol/min will be administered intra-arterially to induce vasoconstriction. Thereafter infusions of apelin (0.1, 1.0, 3.0nmol/min) will be given for 6mins each. During the same study, sodium nitroprusside will given (1.0, 2.0, 4.0 microg/min) for 6mins.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in apelin mediated forearm blood flow |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in local and systemic plasma apelin concentration in response angiotensin II infusion |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renin Angiotensin System