Comparative Effects of Endothelin and Neurotensin on Intrinsic Cardiac Neurons In Situ

Abstract

Studies were performed on anesthetized dogs to determine whether the peptides endothelin and neurotensin influence intrinsic cardiac neurons in situ and, if so, whether intrinsic cardiac neurons sensitive to these peptides are involved in cardiac regulation. Endothelin-1 (0.1 ml, 100 nM), which has high affinity for ETA endothelin receptors, when administered to a population of right atrial neurons via their regional arterial blood supply increased neuronal activity (+173%), heart rate (+18%), as well as right (62%) and left ventricular (14%) intramyocardial systolic pressures in 12 dogs so tested. When the selective ETB endothelin receptor agonist BQ-3020 (0.1 ml, 100 nM) was applied to these neurons their activity increased (+119%) in 10 of 12 dogs tested, as did right (56%) and left (12%) ventricular intramyocardial systolic pressures. Neuronal and cardiac responses were induced by BQ-3020, but not by endothelin-1, in the presence of a selective ETA receptor antagonist (BQ-610). When a greater dose of endothelin-1 (0.1 ml, 10 μM) was administered to right atrial neurons in four separate dogs, alterations in neuronal activity were accompanied by ventricular arrhythmias that progressed to ventricular fibrillation. In contrast, when neurotensin (0.1 ml, 10 μM) was administered into their regional arterial blood supply intrinsic cardiac neurons were excited without cardiac variables being affected. These data indicate that: 1) mammalian intrinsic cardiac neurons are sensitive to endothelin and neurotensin; 2) endothelin-sensitive intrinsic cardiac neurons possess ETA and ETB receptors; 3) cardiac indices are enhanced when intrinsic cardiac neurons sensitive to endothelin, not neurotensin, become activated.