CANINE INTRINSIC CARDIAC NEURONS INVOLVED IN CARDIAC REGULATION POSSESS NK1, NK2 AND NK3 RECEPTORS

To determine whether intrinsic cardiac neurons involved in cardiac reg ulation possess neurokinin (NK) receptor subtypes, we administered sel ective NK receptor agonists individually (100 mu M; 0.1 mi) into the c oronary arterial blood supply of right atrial intrinsic cardiac neuron s of 18 anesthetized dogs. The selective NK1 receptor agonist [Sar(9), Met(O-2)(11)]-substance P depressed the spontaneous activity of right atrial neurons (26.7 +/- 6.7 to 13.0 +/- 4.0 impulses/min; P < 0.05) i n 11 dogs and augmented such activity in the other 5 dogs (8.0 +/- 3.1 to 27.8 +/- 8.7 impulses/ min; P < 0.05). Local administration of the selective NK2 receptor agonist [beta-Ala(8)]-NKA-(4-10) depressed rig ht atrial neuronal activity(27.3 +/- 6.4 to 14.7 +/- 3.8 impulses/min; P < 0.05), whereas the selective NK3 receptor agonist senktide augmen ted such activity (18.9 +/- 6.4 to 53.1 +/- 12.0 impulses/ min; P < 0. 05). Left ventricular chamber pressure fell when selective NK1 and NK2 receptor agonists were administered. Increases in heart rate and righ t ventricular intramyocardial systolic pressure occurred when the sele ctive NK3 receptor agonist was studied. Administration of a selective NK1 or NK2 receptor antagonist altered neuronal activity, with no subs equent change in activity occurring after administration of its respec tive receptor agonist. Receptor autoradiography demonstrated tachykini n receptors associated with ventral right atrial intrinsic cardiac neu rons. It is concluded that intrinsic cardiac neurons involved in cardi ac regulation possess NK1, NK2, and NK3 receptors and that some intrin sic cardiac neurons receive tonic input via endogenously released NKs.