Role of Full and Partial Adenosine Receptor Agonists in the Cardiac Myocyte

Abstract

Cardiovascular disease remains one of the largest health burdens facing the westernised world. The ubiquitous nucleoside, adenosine and its accompanying receptors may have beneficial effects in the treatment of ischaemic heart disease. Adenosine is derived from the catabolism of ATP and has long been considered a potent bradycardic and hypotensive compound. For over half a century, adenosine and its analogues have often been considered potential cardioprotective drug targets. These protective effects are mediated via the action of adenosine receptors: ADORA1, ADORA2A, ADORA2B and ADORA3. The main purpose of this thesis was to examine the role and mechanisms of selective adenosine full and partial agonists in the ischaemic-reperfused mouse heart, exploring the potential cellular mechanisms involved in cardiomyocyte cell death, functional parameters and pharmacological manipulation of the recovering heart. The effects of enhancing endogenous adenosine activation through the use of allosteric enhancers are also assessed.