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. Apelin has the ability to cause blood vessels to relax, increasing their diameter and hence blood flow down the blood vessel. The researchers wish to investigate the hypothesis that an infusion of apelin will reduce the effects of angiotensin II, which is know to reduce the diameter of blood vessels.

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: Angiotensin II
* Drug: Noradrenaline infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 18 years old Healthy volunteers 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: Infusion of apelin<br>Using forearm venous occlusion plethysmography apelin will be infused to cause reduction in forearm blood flow. Infusion of angiotensin II and noradrenaline will given and vasoconstriction 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: Angiotensin II<br>* Infusion of up to 30picmol/ml angiotensin II will be infused and respondent vasoconstriction assessed.<br>Drug: Noradrenaline infusion<br>* Infusion of up to 480 picomol/ml of noradrenaline will be infused.<br>|
| Active Comparator: Sodium nitroprusside infusion<br>Using forearm venous occlusion plethysmography sodium nitroprusside will be infused to cause reduction in forearm blood flow. Infusion of angiotensin II and noradrenaline will given and vasoconstriction 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: Angiotensin II<br>* Infusion of up to 30picmol/ml angiotensin II will be infused and respondent vasoconstriction assessed.<br>Drug: Noradrenaline infusion<br>* Infusion of up to 480 picomol/ml of noradrenaline will be infused.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in angiotensin II mediated vasoconstriction |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in relevant neurohumoral hormones in response to apelin 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, Apelin, Vasodilatation, Heart disease, Vascular biology