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Adenosine receptor interactions alter cardiac contractility in rat heart
Author(s) -
Rose’Meyer Roselyn B
Publication year - 2010
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2009.05228.x
Subject(s) - contractility , adenosine , adenosine receptor , medicine , cardiology , adenosine a1 receptor , receptor , chemistry , endocrinology , agonist
Summary 1. The effect of the adenosine A 2 receptor (AdoA 2 R) agonist N 6 ‐[2‐(3,5‐dimethoxyphenyl)‐2‐(2‐methylphenyl)‐ethyl]adenosine (DPMA) on adenosine A 1 receptor (AdoA 1 R)‐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)‐N 6 ‐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 × d P / d t max ), which were significantly attenuated by 1 nmol / L DPMA with a shift in pEC 50 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 2A R 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 AdoA 1 R‐mediated negative inotropic actions, whereas the AdoA 2B R antagonist alloxazine (3 μmol / L) had no effect on DPMA activity. 4. The results of the present study show that stimulation of the AdoA 2 R attenuates AdoA 1 R‐dependent reductions in inotropic state. The receptor involved appears to be the AdoA 2A R and its action involves stimulation of adenylyl cyclase activity.