Eplerenone and Extracellular Adenosine Formation

• Status: Completed
• Trial end date: 2014-01-01
• Target enrollment: 0
• Participant gender: Male

Summary

Various studies have reported cardioprotective effects of mineralocorticoid receptor (MR) antagonists in the setting of an acute myocardial infarction. In a recent animal study, the protective effect of MR antagonists on infarct size was completely abolished in CD73 knock-out and adenosine A2b receptor knock-out mice, and by co-administration of adenosine receptor antagonists in rats. These findings suggest that extracellular formation of adenosine is crucial for this protective effect and that MR antagonists stimulate extracellular adenosine formation by the enzyme CD73.

To investigate whether eplerenone promotes adenosine receptor stimulation by activating CD73, the investigators will measure forearm blood flow in response to various dosages of dipyridamole with the use of plethysmography. Dipyridamole increases the extracellular endogenous adenosine concentration by inhibition of the ENT transporter and induces local vasodilation. Therefore, the vasodilator effect of dipyridamole accurately reflects extracellular adenosine formation by the CD73 enzyme.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Radboud University
• Treatments: Adenosine; Eplerenone; Mineralocorticoid Receptor Antagonists; Spironolactone

Criteria

Inclusion Criteria:

• Male sex

• Age 18-40 years

• Healthy

• Written informed consent

Exclusion Criteria:

• Smoking

• Hypertension (Blood pressure >140 mmHg and/or >90 mmHg - SBP/DBP-)

• Hypotension (Blood pressure <100 mmHg and/or <60 mmHg -SBP/DBP-)

• Diabetes Mellitus (fasting glucose > 6.9 mmol/L or random > 11.0 mmol/L in venous plasma)

• History of any cardiovascular disease

• Angina pectoris

• History of chronic obstructive pulmonary disease (COPD) or asthma

• Alcohol and/or drug abuse

• Concomitant use of medication

• Renal dysfunction (MDRD < 60 ml/min/1.73 m2)

• Liver enzyme abnormalities (ALAT > twice upper limit of normality)

• Serum potassium ≥ 4.8 mmol/L

• Fasting total cholesterol > 6.0 mmol/L

• Second/third degree AV-block on electrocardiography