Enkephalins, substance P and acetylcholine microinjected into the nucleus ambiguus elicit vagal bradycardia in rats

Little is known about putative transmitters in the nucleus ambiguus (NA) mediating parasympathetic control of the heart, although Metenkephalin (m-ENK), Leu-enkephalin (l-ENK), substance P (SP) and acetylcholine (Ach) have been detected in the cell bodies and fibers of this nucleus. The effects of these substances on arterial pressure (AP) and heart rate (HR) were studied by microinjecting them (4-20 nl) into the NA. Experiments were done in 26 spinal (high cervical) rats that were anesthetized with urethane and artificially ventilated. l-Glutamate (GLU) was microinjected into the right NA to identify the location of cell bodies from which decreases in HR and AP could be elicited. m-ENK, l-ENK, SP or Ach was then microinjected into these sites. Microinjection of 1 nmol of GLU elicited significant decreases in HR (-72.2 ± 9.7 bpm, n = 15) which were not accompanied by significant decreases in mean AP. Microinjection of m-ENK (15-200 pmol; n = 7), l-ENK (15-200 pmol; n = 6), SP (0.9-15 pmol; n = 7) and Ach (2.0-20 pmol; n = 7) into the NA decreased HR in a dose-dependent manner but did not affect AP. The magnitudes of HR responses to m-ENK, l-ENK, SP and Ach were smaller but of longer duration than the changes in HR to microinjection of GLU. These results suggest a physiological role for GLU, enkephalins, SP and Ach in the vagal control of HR mediated by the NA.