The aminotetraline derivative (+/-)-(R,S)-5,6-dihydroxy-2-methylamino-1,2,3,4-tetrahydro-naphthalene hydrochloride (CHF-1024) displays cardioprotection in postischemic ventricular dysfunction of the rat heart.

Abstract

To analyze the protective effects of the aminotetraline derivative (+/-)-(R,S)-5,6-dihydroxy-2-methylamino-1,2,3,4-tetrahydro-naphthalene hydrochloride (CHF-1024), a compound endowed with DA2-dopaminergic/alpha2-adrenergic receptor agonistic activity, in myocardial ischemia/reperfusion damage. A model of isolated and perfused (15 ml/min) electrically driven (300 beats/min) rat heart subjected to global ischemia (1 ml/min for 20 min) and reperfusion (15 ml/min for 30 min) was followed. Cardiac mechanics changes were evaluated together with biochemical markers of cardiac ischemia in perfusate and tissue tumor necrosis factor-alpha (TNF-alpha). CHF-1024, perfused through the heart for 15 min before ischemia at different molar concentrations (1-100 nM), significantly improved left ventricle developed pressure during reperfusion, and normalized left ventricular end-diastolic pressure and coronary perfusion pressure. This anti-ischemic effect of CHF-1024 was associated to a decrease in creatine kinase and lactate dehydrogenase, both released during heart reperfusion. These events were concomitant with maintenance of a higher production of 6-keto-prostaglandin F1alpha The ability of CHF-1024 to improve postischemic ventricular dysfunction was correlated with a dose-dependent inhibition of the release of both norepinephrine (NE), from sympathetic nerve endings, and TNF-alpha from cardiac tissue. The effect of CHF-1024 on NE release was almost completely antagonized by specific antagonists of presynaptic inhibitory receptors domperidone and rauwolscine. The finding that this new aminotetraline derivative possesses anti-ischemic properties and limits NE release from cardiac nerve endings may bear some therapeutic potential in cardiovascular diseases.

• Authors: Giuseppe Rossoni, Barbara Manfredi, Viviana Cavalca, Roberta Razzetti, Stefano Bongrani, Gian Luca Polvani, Ferruccio Berti
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 307 Issue 2 Pg. 633-9 (Nov 2003) ISSN: 0022-3565 [Print] United States
• PMID: 12975493 (Publication Type: Journal Article)

Chemical References

• Cardiotonic Agents
• Tetrahydronaphthalenes
• Tumor Necrosis Factor-alpha
• Epoprostenol
• L-Lactate Dehydrogenase
• Creatine Kinase
• CHF 1024
• Norepinephrine

Topics

• Animals
• Cardiotonic Agents (therapeutic use)
• Creatine Kinase (metabolism)
• Epoprostenol (metabolism)
• Heart (drug effects)
• L-Lactate Dehydrogenase (metabolism)
• Male
• Myocardial Ischemia (complications)
• Myocardial Reperfusion
• Myocardial Reperfusion Injury (etiology, prevention & control)
• Myocardium (metabolism)
• Norepinephrine (metabolism)
• Rats
• Rats, Wistar
• Tetrahydronaphthalenes (therapeutic use)
• Tumor Necrosis Factor-alpha (metabolism)
• Ventricular Dysfunction (etiology, prevention & control)