RT Journal Article
SR Electronic
T1 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
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 633
OP 639
DO 10.1124/jpet.103.054700
VO 307
IS 2
A1 Giuseppe Rossoni
A1 Barbara Manfredi
A1 Viviana Cavalca
A1 Roberta Razzetti
A1 Stefano Bongrani
A1 Gian Luca Polvani
A1 Ferruccio Berti
YR 2003
UL http://jpet.aspetjournals.org/content/307/2/633.abstract
AB 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/α2-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-α (TNF-α). 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 F1α 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-α 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. The American Society for Pharmacology and Experimental Therapeutics