Interaction of Apelin and Angiotensin in the Human Forearm Circulation

NCT00901888 | Completed

• 1 other identifier: FS/09/019/26905 - 1a
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Disease; Vasodilation

Keywords

Renin Angiotensin System

Outcome Measures

Primary Outcomes (1)

• Change in apelin mediated forearm blood flow

  12 months

Secondary Outcomes (1)

• Change in local and systemic plasma apelin concentration in response angiotensin II infusion

  12 months

Study Arms (2)

Angiotensin II infusion

EXPERIMENTAL

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; Drug: Sodium nitroprusside infusion

Noradrenaline

ACTIVE COMPARATOR

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; Drug: Sodium nitroprusside infusion

Interventions

Apelin infusion DRUG

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.

Angiotensin II infusion; Noradrenaline

Sodium nitroprusside infusion DRUG

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.

Angiotensin II infusion; Noradrenaline

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \> 18 years old

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator

Study Sites (1)

Clincial Research Facility, Royal Infirmary of Edinburgh, 51 Little France Cresc

Edinburgh, EH16 4SA, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 23519586 DERIVED

MeSH Terms

Conditions

Heart Diseases; Aneurysm

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Vascular Diseases

Study Officials

• Gareth D Barnes, MBChB

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 8, 2009
• First Posted: May 14, 2009
• Study Start: April 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: August 10, 2010

Record last verified: 2010-08

Locations

GB (1)