5’-Adenosine monophosphate and adenosine metabolism, and adenosine responses in mouse, rat and guinea pig heart

Abstract

We examined myocardial 5′-adenosine monophosphate (5′-AMP) catabolism, adenosine salvage and adenosine responses in perfused guinea pig, rat and mouse heart. MVo2 increased from 71±8 μl O2/min per g in guinea pig to 138±17 and 221±15 μl O2/min per g in rat and mouse. Vo2/beat was 0.42±0.03, 0.50±0.03 and 0.55±0.04 μl O2/g in guinea pig, rat and mouse, respectively. Resting and peak coronary flows were highest in mouse vs. rat and guinea pig, and peak ventricular pressures and Ca2+ sensitivity declined as heart mass increased. Net myocardial 5′-AMP dephosphorylation increased significantly as mass declined (3.8±0.5, 9.0±1.4 and 11.0±1.6 nmol/min per g in guinea pig, rat and mouse, respectively). Despite increased 5′-AMP catabolism, coronary venous [adenosine] was similar in guinea pig, rat and mouse (45±8, 69±10 and 57±14 nM, respectively). Comparable venous [adenosine] was achieved by increased salvage vs. deamination: 64%, 41% and 39% of adenosine formed was rephosphorylated while 23%, 46%, and 50% was deaminated in mouse, rat and guinea pig, respectively. Moreover, only 35–45% of inosine and its catabolites derive from 5′-AMP (vs. IMP) dephosphorylation in all species. Although post-ischemic purine loss was low in mouse (due to these adaptations), functional tolerance to ischemia decreased with heart mass. Cardiovascular sensitivity to adenosine also differed between species, with A1 receptor sensitivity being greatest in mouse while A2 sensitivity was greatest in guinea pig. In summary: (i) cardiac 5′-AMP dephosphorylation, Vo2, contractility and Ca2+ sensitivity all increase as heart mass falls; (ii) adaptations in adenosine salvage vs. deamination limit purine loss and yield similar adenosine levels across species; (iii) ischemic tolerance declines with heart mass; and (iv) cardiovascular sensitivity to adenosine varies, with increasing A2 sensitivity relative to A1 sensitivity in larger hearts.