Mechanisms involved in adenosine pharmacological preconditioning-induced cardioprotection

Abstract

Adenosine is a naturally occurring breakdown product of adenosine triphosphate and plays an important role in different physiological and pathological conditions. Adenosine also serves as an important trigger in ischemic and remote preconditioning and its release may impart cardioprotection. Exogenous administration of adenosine in the form of adenosine preconditioning may also protect heart from ischemia-reperfusion injury. Endogenous release of adenosine during ischemic/remote preconditioning or exogenous adenosine during pharmacological preconditioning activates adenosine receptors to activate plethora of mechanisms, which either independently or in association with one another may confer cardioprotection during ischemia-reperfusion injury. These mechanisms include activation of KATP channels, an increase in the levels of antioxidant enzymes, functional interaction with opioid receptors; increase in nitric oxide production; decrease in inflammation; activation of transient receptor potential vanilloid (TRPV) channels; activation of kinases such as protein kinase B (Akt), protein kinase C, tyrosine kinase, mitogen activated protein (MAP) kinases such as ERK 1/2, p38 MAP kinases and MAP kinase kinase (MEK 1) MMP. The present review discusses the role and mechanisms involved in adenosine preconditioning-induced cardioprotection.

Conditioning attenuates kidney and heart injury in rats following transient suprarenal occlusion of the abdominal aorta

“…Previous studies have demonstrated that mitochondrial KATP channel activity and adenosine signaling exert a protective effect during IRI 9,35,36,51 . Induction of these molecular routes exert an immunomodulatory and anti-oxidant effect in different models of IRI [52][53][54][55] .…”

“…www.nature.com/scientificreports www.nature.com/scientificreports/ Treatment with 5-HD or 8-SPT abolishes the protective effect of conditioning. Earlier studies have shown that administering the KATP channel blocker 5-HD or the non-selective adenosine inhibitor 8-SPT, eliminates the protective effect of IPre and IPost 35,36 . To decipher the role of mitochondrial KATP channel activity and adenosine signaling in this context, we administered 5-HD or 8-SPT before the application of suprarenal abdominal artery occlusion and reperfusion (Fig.…”

Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs

“…Directly acting, potent agonists (1-15) and antagonists (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) for each of the ARs are available as pharmacological probes, and, in several cases, agents approved for human use ( Figure 2) [22]. AR agonists 1 (adenosine) and 9 (regadenoson) and are approved for clinical use in myocardial perfusion diagnostics and/or supraventricular tachycardia diagnosis and treatment.…”

“…Ischemic preconditioning of the heart, i.e., when short ischemic episodes improve the outcome of a subsequent ischemia event, is thought to involve ARs, consistent with the highly elevated levels of adenosine that occur in hypoxia. Preconditioning can also be induced by exogenous AR agonists, potentially through activation of each of the four AR subtypes, which are present on cardiac myocytes [34,35]. Adenosine pretreatment also conditions against ischemic cardiac damagẽ 24-72 h later [36].…”

Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs

“…Ischemic preconditioning of the heart, when a pretreatment improves the outcome from an ischemia event, is thought to involve ARs, consistent with the highly elevated levels of adenosine that occur in hypoxia. Preconditioning can also be induced by exogenous AR agonists, potentially through activation of each of the four AR subtypes, which are present on cardiac myocytes (Cohen et al, 2010;Singh et al, 2018;Wan et al, 2019). Adenosine pretreatment also conditions against ischemic cardiac damage ~24-72 hours later (Baxter, 2002).…”