Aged rat myocardium exhibits normal adenosine receptor-mediated bradycardia and coronary vasodilation but increased adenosine agonist-mediated cardioprotection.
The purpose of this study was to determine whether aged myocardium exhibits decreased responsiveness to adenosine A1 and A(2a) receptor activation. Studies were conducted in adult (4-6 months) and aged (24-26 months) Fischer 344 x Brown Norway hybrid (F344 x BN) rats. Effects of the adenosine A1/A(2a) agonist AMP579 were measured in isolated hearts and in rats submitted to in vivo regional myocardial ischemia. Aged isolated hearts exhibited lower spontaneous heart rates and higher coronary resistance, as well as normal A1- and A(2a)-mediated responses. There was no difference in control infarct size between adult and aged rats; however, AMP579 treatment resulted in a 50% greater infarct size reduction in aged rats (18 +/- 4% of risk area) compared to adult rats (37 +/- 3%). These findings suggest that adenosine A1 and A(2a) receptor-mediated effects are not diminished in normal aged myocardium, and that aged hearts exhibit increased adenosine agonist-induced infarct reduction.
Kristo
Gentian
G
Department of Surgery, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536-0298, USA.
Yoshimura
Yukihiro
Y
Keith
Byron J
BJ
Mentzer
Robert M
RM
Lasley
Robert D
RD
D000375:Aging / Q000502:physiology*; D000818:Animals; D001919:Bradycardia / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006321:Heart / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
C113971:4-(7-((2-3-chloro-2-thienyl)-1-methyl-propylamino)-3H-imidazo(4,5-b)pyridyl-3-yl)cyclopentane carboxamide; D002316:Cardiotonic Agents; D007093:Imidazoles; D058906:Purinergic P1 Receptor Agonists; D011725:Pyridines; D018047:Receptors, Purinergic P1