Interaction of Apelin and Angiotensin in the Human Forearm Circulation

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.

• Heart Disease
• Vasodilation

• Drug: Apelin infusion
  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.
• Drug: Sodium nitroprusside infusion
  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.

• Experimental: Angiotensin II infusion
  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.
  Interventions:

  • Drug: Apelin infusion
  • Drug: Sodium nitroprusside infusion
• Active Comparator: Noradrenaline
  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.
  Interventions:

  • Drug: Apelin infusion
  • Drug: Sodium nitroprusside infusion

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