Effects of endogenous adenosine and adenosine receptor agonists on hypoxia-induced myocardial stunning in Guinea-pig atria and papillary muscles.
The effects of endogenous adenosine and adenosine receptor agonists were examined on hypoxia-induced myocardial stunning of guinea-pig isolated paced left atria and papillary muscles. Hypoxia (30 minutes) reduced developed tension and increased diastolic tension (contracture) of left atria (41.8 +/- 11.5%) and papillary muscles (17.7 +/- 6.2%). Developed tension recovered to 80.8 +/- 3.15 and 77.2 +/- 5.3% 15 minutes after reoxygenation (stunning). Recovery of left atria was unaffected by adenosine deaminase (1 IU mL) but was depressed in papillary muscles (15 minutes, 48.6 +/- 4.3%) and contracture (46.1 +/- 7.5%) increased. Endogenous adenosine therefore protects from ventricular but not atrial stunning. Adenosine receptor agonists were introduced at 10 minutes into hypoxia. CPA (A1 selective, 3 x 10 M) impaired left atrial recovery (5 minutes, 38.1 +/- 5.0%), through direct negative inotropy, but did not affect papillary muscles. CGS21680 (A2A selective, 3 x 10 M) did not affect recovery. APNEA (A1/A3 receptor agonist, 10 M), increased recovery rate of left atria. Improved rate and extent of recovery of papillary muscles by APNEA (15 minutes, 94.8 +/- 3.1%) was prevented by the A3 receptor antagonist, MRS-1220 (10 M). IB-MECA (A3 selective, 3 x 10 M) increased atrial recovery rate but not the maximum developed tension reached in either tissue. However, when added at reoxygenation, IB-MECA caused complete recovery of both tissues, in the absence or presence of adenosine deaminase. Thus, A3 receptor stimulation reverses myocardial stunning of isolated atria and papillary muscles.
Gardner
Neil M
NM
Division of Pharmacology, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cathays Park, Cardiff, UK.
Yates
Lisa
L
Broadley
Kenneth J
KJ
D000241:Adenosine / Q000502:physiology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects*; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D017682:Myocardial Stunning / Q000209:etiology / Q000517:prevention & control*; D010210:Papillary Muscles / Q000187:drug effects; D058906:Purinergic P1 Receptor Agonists
D058906:Purinergic P1 Receptor Agonists; D000243:Adenosine Deaminase; D000241:Adenosine