Impact and mechanisms of action of neurotensin on cardiac contractility in the rat left ventricle.
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. EC(50) 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 beta-adrenoceptor antagonists, but not by histamine, serotonin or angiotensin II receptor antagonists. In conclusion, neurotensin increases ventricular contractility through stimulation of myocardial norepinephrine release.
Osadchii
Oleg
O
Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand, Medical School, Johannesburg, South Africa. osadchii@mail.ru
Norton
Gavin
G
Deftereos
Dawn
D
Badenhorst
Danelle
D
Woodiwiss
Angela
A
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003326:Coronary Circulation; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000737:chemistry; D006352:Heart Ventricles / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009496:Neurotensin / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010477:Perfusion; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors; D016277:Ventricular Function, Left / Q000187:drug effects*
D002316:Cardiotonic Agents; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C079087:SR 48692; D009496:Neurotensin; D009638:Norepinephrine