In the heart, A1 receptors play roles in electrical pacing (
chronotropy and
dromotropy), fluid balance, local sympathetic regulation, and metabolism. Adenosine agonism of A1ARs also inhibits release of
norepinephrine from cardiac nerves. Norepinephrine is a positive chronotrope,
inotrope, and dromotrope, through its agonism of β adrenergic receptors on
pacemaker cells and ventricular myocytes. Collectively, these mechanisms lead to an myocardial depressant effect by decreasing the conduction of electrical impulses and suppressing
pacemaker cells function, resulting in a decrease in
heart rate. This makes adenosine a useful medication for treating and diagnosing
tachyarrhythmias, or excessively fast heart rates. This effect on the A1 receptor also explains why there is a brief moment of cardiac standstill when adenosine is administered as a rapid
IV push during
cardiac resuscitation. The rapid infusion causes a momentary myocardial stunning effect. In normal physiological states, this serves as protective mechanisms. However, in altered cardiac function, such as
hypoperfusion caused by
hypotension,
heart attack or
cardiac arrest caused by nonperfusing
bradycardias, adenosine has a negative effect on physiological functioning by preventing necessary compensatory increases in heart rate and blood pressure that attempt to maintain cerebral perfusion. Metabolically, A1AR activation by endogenous adenosine across the body reduces plasma
glucose,
lactate, and
insulin levels, however
A2aR activation increased glucose and lactate levels to an extent greater than the A1AR effect on glucose and lactate. Thus, intravascular administration of adenosine increases the amount of glucose and lactate available in the blood for cardiac myocytes. A1AR activation also partially inhibits
glycolysis, slowing its rate to align with oxidative metabolism, which limits post-ischemic damage through reduced H+ generation. In the state of myocardial hypertrophy and remodeling, interstitial adenosine and the expression of the A1AR receptor are both increased. After transition to heart failure however, overexpression of A1AR is no longer present. Excess A1AR expression can induce cardiomyopathy, cardiac dilatation, and cardiac hypertrophy. Cardiac failure may involve increased A1AR expression and decreased adenosine in physical models of cardiac overload and in dysfunction induced by TNFα. Heart failure often involves secretion of atrial natriuretic peptide to compensate for reduced renal perfusion and thus, secretion of electrolytes. A1AR activation also increases secretion of atrial natriuretic peptide from atrial myocytes. == References ==