Impact and mechanisms of action of neurotensin on cardiac contractility in the rat left ventricle
European Journal of Pharmacology
Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, South Africa
Using immunoassay measurements, neurotensin was identified in rat ventricular tissue and in coronary effluent samples. Exogenous neurotensin evoked contractile responses in isolated ventricular preparations, which were equivalent in magnitude to those of norepinephrine and histamine, but greater than those for serotonin and angiotensin II. EC50 values revealed neurotensin to be as potent as serotonin, but more potent than norepinephrine, histamine and angiotensin II. Structure-activity studies indicated that the contractile effects are attributed to the C-terminal portion of neurotensin. Neurotensin-induced responses were decreased by SR 48692, a specific neurotensin receptor antagonist. Neurotensin elicited an increase in coronary effluent norepinephrine concentrations, and a strong relationship between the magnitude of neurotensin-induced contractile effects and increments in myocardial norepinephrine release were noted. Neurotensin-induced contractile responses were abolished by β-adrenoceptor antagonists, but not by histamine, serotonin or angiotensin II receptor antagonists. In conclusion, neurotensin increases ventricular contractility through stimulation of myocardial norepinephrine release. © 2005 Elsevier B.V. All rights reserved.
2 [[1 (7 chloro 4 quinolinyl) 5 (2,6 dimethoxyphenyl) 3 pyrazolyl]carbonylamino] 2 adamantanecarboxylic acid; angiotensin; angiotensin II antagonist; antihistaminic agent; beta adrenergic receptor blocking agent; histamine; inotropic agent; neurotensin; neurotensin receptor antagonist; noradrenalin; serotonin; serotonin antagonist; animal tissue; article; beta adrenergic receptor blocking; carboxy terminal sequence; comparative study; concentration response; controlled study; drug activity; drug effect; drug inhibition; drug mechanism; drug potency; evoked muscle response; heart left ventricle contractility; heart muscle contractility; heart stimulation; immunoassay; inotropism; isolated heart; male; nonhuman; noradrenalin release; pathophysiology; priority journal; rat; structure activity relation; Animals; Cardiotonic Agents; Coronary Circulation; Dose-Response Relationship, Drug; Extracellular Fluid; Heart Ventricles; Male; Myocardial Contraction; Neurotensin; Norepinephrine; Perfusion; Pyrazoles; Quinolines; Rats; Rats, Sprague-Dawley; Receptors, Neurotensin; Ventricular Function, Left