Histamine-sensitive intrinsic cardiac and intrathoracic extracardiac neurons influence cardiodynamics

Abstract

Studies were performed to determine whether 1) histamine can modify the spontaneous activity of mammalian intrinsic cardiac neurons in situ, 2) histamine-sensitive neurons exist in intrathoracic intrinsic cardiac and extracardiac ganglia that are involved in cardiac regulation, and 3) histamine-sensitive intrathoracic cardiac neurons possess H1 or H2 receptors. histamine (10 microliters; 100 microM), when applied adjacent to spontaneously active canine right atrial neurons in situ, increased ongoing activity in some of them. Histamine, when administered into the local arterial blood supply of these neurons (0.1 ml; 100 microM) not only increased their activity but induced cardiac augmentation. Cardioaugmentor responses were also elicited when histamine (10 microliters or 0.1 ml; 100 microM) was administered into limited loci within stellate and middle cervical ganglia that were connected to the heart, but not in ganglia surgically disconnected the heart. Neuronal and cardiac responses no longer were elicited after local administration of the H1-selective receptor antagonist triprolidine. They were unaffected by local application of the H2-selective receptor antagonist cimetidine. No cardiac augmentation was elicited when histamine was applied to intrathoracic autonomic neurons following timolol (1 mg/kg i.v.) administration. These data indicate that 1) histaminergic neurons exist in intrinsic cardiac and intrathoracic extracardiac ganglia that are involved in cardiac regulation, 2) these neurons possess H1 receptors, and 3) histamine-sensitive intrathoracic neurons directly or indirectly activate cardiac adrenergic neurons, thereby inducing cardiac augmentation