Pharmacodynamics Clinical Trial
Official title:
Effects of the Selective Mineralocorticoid Receptor Antagonist Eplerenone on Extracellular Adenosine Formation in Humans in Vivo
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.
n/a
Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science
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