Hemodynamic changes do not mediate the cardioprotection induced by the A1, adenosine receptor agonist CCPA in the rabbit.
Stimulation of adenosine A1 receptors is known to reduce infarct size in the rabbit heart. The aim of the present study was to verify whether a protective activity similar to that of the selective A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA), could also be obtained by inducing comparable hemodynamic effects with drugs having different mechanisms of action. The effects of the beta-adrenoceptor blocker atenolol, the calcium channel blocker felodipine, the A2A-selective adenosine receptor agonist 2-hexynyl-5'-N-ethyl-carboxamidoadenosine (2HE-NECA), and the non-selective adenosine receptor agonist 5'-N-ethyl-carboxamidoadenosine (NECA) were tested. Groups of 12-15 anesthetized open-chest rabbits received a 5-min infusion of CCPA (50 micrograms kg-1 min-1), atenolol (1 mg kg-1 min-1), felodipine (50 micrograms kg-1 min-1), 2HE-NECA (1 microgram kg-1 min-1), and NECA ( 1 microgram kg-1 min-1). Myocardial infarction was induced by a 30-min occlusion of a branch of the left coronary artery, followed by 3-h reperfusion. Infarct size was measured by tetrazolium staining. In controls, infarct size was about 40% of the zone at risk. Pretreatment with CCPA induced a marked decrease in heart rate (-40%) and blood pressure (-48%), and showed antiischemic activity (28% of the zone at risk). The other drugs tested produced similar effects on either heart rate (atenolol, -25%), or blood pressure (felodipine, 2HE-NECA and NECA, about -45%), but did not affect infarct size. IN this model, the reduction in infarct size by CCPA is most likely mediated by A1 receptors, since comparable hemodynamic effects, induced by other means, are not effective. A2A receptor stimulation does not appear to exert a protective effect.
Casati
C
C
Schering-Plough Research Institute, Milan, Italy.
Forlani
A
A
Lozza
G
G
Monopoli
A
A
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019830:Adenosine-5'-(N-ethylcarboxamide); D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015736:Felodipine / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D058906:Purinergic P1 Receptor Agonists; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D058906:Purinergic P1 Receptor Agonists; D014665:Vasodilator Agents; D019830:Adenosine-5'-(N-ethylcarboxamide); C058394:2-chloro-N(6)cyclopentyladenosine; D001262:Atenolol; D000241:Adenosine; D015736:Felodipine