Solitarius to Stimulation of Heart and Lung Receptors in the Rat

To characterize central integration of reflex responses to stimulation of mechanically and chemically sensitive receptors in the heart and lung, male rats (350 to 425 g) were anesthetized (pentobarbital, 50 mg/kg IP) and paralyzed (gallamine triethiodide, 25 mg/kg IV), and then they underwent bilateral sinoaortic denervation. Extracellular activity of neurons in the nucleus tractus solitarius (NTS) was recorded in response to bolus intra-atrial saline (50, 100, 200, or 300 gtL) or phenylbiguanide (PBG, 16 gLg/kg in 100 ,L) administered in random sequence. Changes in mean arterial pressure (MAP), mean right atrial pressure, and right atrial systolic pressure (RASP) were measured as correlates of stimulus intensity, and heart rate (HR) and renal sympathetic nerve activity (RSNA) were used to assess efferent reflex effects of cardiac and pulmonary receptor stimulation. NTS neurons with possible afferent input from stretch and chemically sensitive receptors were identified by an excitatory evoked response to electrical stimulation of the ipsilateral vagus nerve (1 Hz, 500 ,uA, 1-millisecond duration). Thirty-eight vagus nerve-evoked NTS units with onset latencies of 25.3+0.9 milliseconds displayed excitatory or inhibitory responses to saline or PBG injections or to both interventions. Saline administration elicited volume-dependent transient increases I t is known that either mechanical or chemical stimulation of certain cardiac and pulmonary receptors elicits reflex cardiovascular effects, which include hypotension, bradycardia, and reduction of efferent sympathetic nerve activity.1-6 Mechanically sensitive cardiac receptors, which mediate these reflex effects, are responsive to changes in blood volume and are located in all chambers of the heart.1-3 Chemically sensitive receptors, responsive to agents such as serotonin and phenylbiguanide (PBG), have also been identified in both atria and ventricles.'-3 Nonmyelinated or lightly myelinated afferent fibers from both mechanically and chemically sensitive receptors project in the vagus nerve and terminate primarily in the nucleus tractus solitarius (NTS).4,7 Although the generalized reflex responses to stimulation of mechanically and chemically sensitive receptors lead to the conclusion that the NTS processes these signals rather nonspecifically, there is evidence to suggest divergence of efferent Received June 25, 1993; accepted February 2, 1994. From the Department of Pharmacology, University of Texas Health Science Center at San Antonio. Correspondence to Tina Hines, PhD, Department of Pharmacology, UTHSCSA, 7703 Floyd Curl Dr, San Antonio, TX 78284-7764. in MAP and RASP, which were followed by reflex decreases in MAP, HR, and RSNA. PBG injections also evoked hypotension, bradycardia, and sympathoinhibition. In contrast to the graded effects of graded saline injections on MAP, right atrial pressure, HR, and RSNA, the mean change in peak NTS cell activity after saline injections did not correlate with the volume injected; rather, the cells responded at one volume threshold and did not alter firing when stimulus intensity (ie, the volume injected) was increased. Although the number of NTS units with firing thresholds at the respective volumes was fairly evenly distributed, the total number of cells responding at any given volume was greater as the volume injected increased. Thus, the graded reflex effects observed during volume expansion may involve recruitment of a progressively greater number of responsive neurons and not graded increases in the discharge frequency of any particular NTS cell. These data indicate a high degree of neural integration in the NTS, which may be critical for the reflex adjustments to stimulation of mechanically and chemically sensitive receptors. (Circ Res. 1994;74:1188-1196.)