Adenosine receptor interactions alter cardiac contractility in rat heart

1. The effect of the adenosine A₂ receptor (AdoA₂R) agonist N⁶‐[2‐(3,5‐dimethoxyphenyl)‐2‐(2‐methylphenyl)‐ethyl]adenosine (DPMA) on adenosine A₁ receptor (AdoA₁R)‐mediated negative inotropic responses was investigated in rat heart. 2. Hearts from male Wistar rats (250–350 g) were perfused with Krebs’–Henseleit solution at constant flow in non‐recirculating Langendorff mode. Hearts were paced at 5 Hz (5 ms duration, supramaximal voltage) via ventricular electrodes. After 30 min equilibration, (R)‐N⁶‐phenylisopropyl adenosine (R‐PIA) concentration–response curves were constructed in the absence or presence of DPMA. 3. In paced hearts, R‐PIA induced concentration‐dependent decreases in triple product (heart rate × peak systolic developed pressure × dP / dt_max), which were significantly attenuated by 1 nmol / L DPMA with a shift in pEC₅₀ from 8.0 ± 0.5 (n = 9) in control hearts to 6.63 ± 1.03 (n = 5) in treated tissues (P < 0.05). The AdoA_2AR antagonist 8‐(3‐chlorostyryl)caffeine (1 μmol / L) and the adenylyl cyclase inhibitor cis‐N‐(2‐phenylcyclopentyl)‐azacyclotridec‐1‐en‐2‐amine hydrochloride (MDL12330A; 100 nmol / L) reversed the effects of DPMA on AdoA₁R‐mediated negative inotropic actions, whereas the AdoA_2BR antagonist alloxazine (3 μmol / L) had no effect on DPMA activity. 4. The results of the present study show that stimulation of the AdoA₂R attenuates AdoA₁R‐dependent reductions in inotropic state. The receptor involved appears to be the AdoA_2AR and its action involves stimulation of adenylyl cyclase activity.