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Published on: August 16, 2016
6-Nitrodopamine Is the Most Potent Endogenous Positive Inotropic Agent in the Isolated Rat Heart
José Britto-Júnior1, Lincoln Rangel Medeiros-Teixeira1, Antonio Tiago Lima1
1Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-970, Brazil.
Background:
6-nitrodopamine released from rat isolated atria exerts positive chronotropic action, being more potent than noradrenaline, adrenaline, and dopamine. Here, we determined whether 6-nitrodopamine is released from rat isolated ventricles (RIV) and modulates heart inotropism.
Methods:
Catecholamines released from RIV were quantified by LC-MS/MS and their effects on heart inotropism were evaluated by measuring left ventricular developed pressure (LVDP) in Langendorff's preparation.
Results:
6-nitrodopamine was the major released catecholamine from RIV. Incubation with L-NAME (100 µM), but not with tetrodotoxin (1 µM), caused a significant reduction in 6-nitrodopamine basal release. 6-nitrodopamine release was significantly reduced in ventricles obtained from L-NAME chronically treated animals. 6-nitrodopamine (0.01 pmol) caused significant increases in LVDP and dP/dtmax, whereas dopamine and noradrenaline required 10 pmol, and adrenaline required 100 pmol, to induce similar increases in LVDP and dP/dtmax. The infusion of atenolol (10 nM) reduced basal LVDP and blocked the increases in LVDP induced by 6-ND (0.01 pmol), without affecting the increases in LVDP induced by 10 nmol of dopamine and noradrenaline and that induced by adrenaline (100 nmol).
Conclusions:
6-nitrodopamine is the major catecholamine released from rat isolated ventricles. It is 1000 times more potent than dopamine and noradrenaline and is selectively blocked by atenolol, indicating that 6-ND is a main regulator of heart inotropism.
