HISTAMINE-SENSITIVE INTRINSIC CARDIAC AND INTRATHORACIC EXTRACARDIAC NEURONS INFLUENCE CARDIODYNAMICS

Studies were performed to determine whether 1) histamine can modify th e spontaneous activity of mammalian intrinsic cardiac neurons in situ, 2) histamine-sensitive neurons exist in intrathoracic intrinsic cardi ac and extracardiac ganglia that are involved in cardiac regulation, a nd 3) histamine-sensitive intrathoracic cardiac neurons possess H-1 or H-2 receptors. Histamine (10 mu l; 100 mu M), when applied adjacent t o spontaneously active canine right atrial neurons in situ, increased ongoing activity in some of them. Histamine, when administered into th e local arterial blood supply of these neurons (0.1 ml; 100 mu M), not only increased their activity but induced cardiac augmentation. Cardi oaugmentor responses were also elicited when histamine (10 mu l or 0.1 ml; 100 mu M) was administered into limited loci within stellate and middle cervical ganglia that were connected to the heart, but not in g anglia surgically disconnected from the heart. Neuronal and cardiac re sponses no longer were elicited after local administration of the Hi-s elective receptor antagonist triprolidine. They were unaffected by loc al application of the H-2-selective receptor antagonist cimetidine. No cardiac augmentation was elicited when histamine was applied to intra thoracic autonomic neurons following timolol (1 mg/kg iv) administrati on. These data indicate that 1) histaminergic neurons exist in intrins ic cardiac and intrathoracic extracardiac ganglia that are involved in cardiac regulation, 2) these neurons possess H-1 receptors, and 3) hi stamine-sensitive intrathoracic neurons directly or indirectly activat e cardiac adrenergic neurons, thereby inducing cardiac augmentation.