Cardioprotective effects of adenosine A1 and A2A receptor agonists in the isolated rat heart.

Abstract

It has been postulated that the adenosine A1 receptor subtype, but also A2a receptors, are involved in mediating the beneficial properties of adenosine during ischemia and reperfusion. We investigated the effects of the selective A1 adenosine receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA), the selective A2A adenosine receptor agonists, 2-[p-(2-carboxyethyl)phenetylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680), 2-hexynyl-5'-N-ethylcarboxamidoadenosine (2HE-NECA), and the non selective agonist, 5'-N-ethylcarboxamidoadenosine (NECA), on ischemia-reperfusion injury in Langendorff-perfused rat hearts. Global ischemia was induced for 15 min in paced hearts followed by 60 min reperfusion. Control hearts developed left ventricular dysfunction, as indicated by the increase in end diastolic pressure to 40.8 +/- 5.1 vs 5.9 +/- 1.0 mm Hg baseline, and in coronary perfusion pressure to 57.6 +/- 8.4 vs 28.8 +/- 2.2 mm Hg before ischemia. After 15 min of reperfusion, ventricular function (LVDP) recovered by 83%, but creatine kinase levels were still significantly increased (294 +/- 55 IUl(-1) vs basal), indicating the occurrence of myocardial injury. All adenosine agonists added to the perfusion medium 15 min prior to ischemia exerted protective effects against myocardial dysfunction and reperfusion injury. Thus, 2HE-NECA (100 nM), CGS 21680 (10 nM), CCPA (3 nM) and NECA (100 nM) significantly (P < 0.05) decreased end diastolic pressure by 50-75% as compared with the control group. Similarly, all compounds significantly (P < 0.05) reduced coronary perfusion pressure by 30-45% vs control. For all drugs, recovery of LVDP occurred immediately after restoration of coronary flow. At 15-min reperfusion the adenosine agonists decreased myocardial creatine kinase release by 80-95% (P < 0.05 vs control). These findings indicate that both A1 and A2A adenosine receptors are involved in protecting the myocardium against ischemia and reperfusion in isolated rat heart, even if through different mechanisms.

• Authors: G Lozza, A Conti, E Ongini, A Monopoli
• Journal: Pharmacological research (Pharmacol Res) Vol. 35 Issue 1 Pg. 57-64 (Jan 1997) ISSN: 1043-6618 [Print] Netherlands
• PMID: 9149317 (Publication Type: Journal Article)

Chemical References

• Antihypertensive Agents
• Phenethylamines
• Purinergic P1 Receptor Agonists
• Receptors, Purinergic P1
• Vasodilator Agents
• 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
• 2-chloro-N(6)cyclopentyladenosine
• Creatine Kinase
• Adenosine

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Analysis of Variance
• Animals
• Antihypertensive Agents (pharmacology)
• Creatine Kinase (blood)
• Male
• Phenethylamines (pharmacology)
• Purinergic P1 Receptor Agonists
• Rats
• Rats, Sprague-Dawley
• Receptors, Purinergic P1 (physiology)
• Reperfusion Injury (physiopathology, prevention & control)
• Vasodilator Agents (pharmacology)