Letters To The Editor The following is the abstract of the article discussed in the subsequent letters. Ferreira, Manuel, Jr., Niaz Sahibzada, Min Shi, Mark Niedringhaus, Matthew R. Wester, Allison R. Jones, Joseph G. Verbalis, and Richard A. Gillis. Hindbrain chemical mediators of reflex-induced inhibition of gastric tone produced by esophageal distension and intravenous nicotine. Am J Physiol Regul Integr Comp Physiol 289: R1482–R1495, 2005. doi:10.1152/ajpregu.00584.2005.— The purpose of this study was to activate a vagovagal reflex by using esophageal distension and nicotine and test whether hindbrain nitric oxide and norepinephrine are involved in this reflex function. We used double-labeling immunocytochemical methods to determine whether esophageal distension (and nicotine) activates c-Fos expression in nitrergic and noradrenergic neurons in the nucleus tractus solitarii (NTS). We also studied c-Fos expression in the dorsal motor nucleus of the vagus (DMV) neurons projecting to the periphery. Esophageal distension caused 19.7  2.3% of the noradrenergic NTS neurons located 0.60 mm rostral to the calamus scriptorius (CS) to be activated but had little effect on c-Fos in DMV neurons. Intravenous adminis- tration of nicotine caused 19.7  4.2% of the noradrenergic NTS neurons 0.90 mm rostral to CS to be activated and, as reported previously, had no effect on c-Fos expression in DMV neurons. To determine whether norepinephrine and nitric oxide were central me- diators of esophageal distension-induced decrease in intragastric pres- sure (balloon recording), N G -nitro-L-arginine methyl ester microin- jected into the NTS (n = 5), but not into the DMV, blocked the vagovagal reflex. Conversely,  2 -adrenergic blockers microinjected into the DMV (n = 7), but not into the NTS, blocked the vagovagal reflex. These data, in combination with our earlier pharmacological microinjection data with nicotine, indicate that both esophageal dis- tension and nicotine produce nitric oxide in the NTS, which then activates noradrenergic neurons that terminate on and inhibit DMV neurons. Comments on “Hindbrain chemical mediators of reflex- induced inhibition of gastric tone produced by esophageal distension and intravenous nicotine” To the Editor: A recent paper published by the research group of Richard Gillis (4) takes issue with our published work (5–7). Gillis’ group contends that  1 -modulation of noradrenergic pathways in the brain stem is not important to the gastric relaxatory reflex evoked by esophageal distension. They fur- ther claim that gastric relaxation provoked by esophageal distension is caused only by withdrawal of vagal cholinergic excitatory activity via  2 -adrenoceptor activation; there is no NANC involvement. Our work (5–7) shows that noradrenergic neurons in the NTS activate both  1 - and  2 -adrenoreceptors in DMV to produce the esophageal gastric reflex via withdrawal of vagal cholinergic excitatory activity ( 2 -mediated) and ac- tivation of NANC activity ( 1 -mediated). There are a number of reasons for a divergence of experimental data; the most significant has to do with physiological technique. The authors claim that the “specific purpose of the present study was to employ the same reflex stimulating technique as Rogers et al....” This is not the case. The stimulating techniques used in these two studies are not comparable. Stimulation parameters used by our group were designed to mimic swallowing of a meal bolus: catheter 2.5 mm diameter, 160 ml distended volume (3). In contrast, Gillis’ group used a balloon distender with 10 mm diameter, 700 ml volume, i.e., a condition far from physiologic (3). The results of these high-amplitude stimuli are reflected in their raw motility records (see Figs. 1 and 2 of Ref. 4) where a sharp gastric contraction occurs during distension and relax- ation occurs after the stimulation is released. These records contrast with our data showing only a relaxation in response to limited esophageal stimulation (6, 7). Instead, Gillis’ responses are similar to those reported by Andrews et al. (1, 2) showing that proximal gastric distension provokes a vagally-mediated increase in gastric tone. Unlike our observations, Gillis group’s observations on the effects of esophageal distension are con- taminated by this increase in gastric tone, probably the result of faulty cannula placement and/or overlarge stimuli. Their fail- ure to observe involvement of an  1 -mediated noradrenergic reflex mechanism is probably the result of this inadvertent elicitation of two essentially antagonistic mechanisms. REFERENCES 1. Andrews PL, Grundy D, and Scratcherd T. Reflex excitation of antral motility induced by gastric distension in the ferret. J Physiol 298: 79 – 84, 1980. 2. Andrews PL, Grundy D, and Scratcherd T. Vagal afferent discharge from mechanoreceptors in different regions of the ferret stomach. J Physiol 298: 513–524, 1980. 3. Dong H, Loomis CW, and Bieger D. Vagal afferent input determines the volume dependence of rat esophageal motility patterns. Am J Physiol Gastrointest Liver Physiol 281: G44 –G53, 2001. 4. Ferreira M Jr, Sahibzada N, Shi M, Niedringhaus M, Wester MR, Jones AR, Verbalis JG, and Gillis RA. Hindbrain chemical mediators of reflex-induced inhibition of gastric tone produced by esophageal distension and intravenous nicotine. Am J Physiol Regul Integr Comp Physiol 289: R1482–R1495, 2005. 5. Guo JJ, Browning KN, Rogers RC, and Travagli RA. Catecholaminergic neurons in rat dorsal motor nucleus of vagus project selectively to gastric corpus. Am J Physiol Gastrointest Liver Physiol 280: G361–G367, 2001. 6. Rogers RC, Hermann GE, and Travagli RA. Brainstem pathways re- sponsible for oesophageal control of gastric motility and tone in the rat. J Physiol 514: 369 –383, 1999. 7. Rogers RC, Travagli RA, and Hermann GE. Noradrenergic neurons in the rat solitary nucleus participate in the esophageal-gastric relaxation reflex. Am J Physiol Regul Integr Comp Physiol 285: R479 –R489, 2003. Richard C. Rogers Gerlinda E. Hermann R. Alberto Travagli Department of Neuroscience Pennington Biomedical Research Center Louisiana State University System Baton Rouge, Louisiana REPLY To the Editor: Rogers et al. (3) raise the issue that the esophageal stimulation techniques used in their studies and ours are not comparable. The purpose of our study (2) was to employ a similar esophageal reflex-stimulating technique as Rogers et al. (3). Although the general method was the same, the stimulation parameters were different (indicated on page R1491 of Ref. 2). This was because the stimulation parameters were dictated by the end point of the response that was measured. As a marker of gastric relaxation evoked by esoph- ageal distension, we used a decrease in intragastric pressure (via balloon recording). Using this end point, esophageal dis- tension of 0.2 ml failed to elicit a significant effect on intra- gastric pressure (see Fig. 1 of Ref. 2) in our experimental preparation. A decrease in intragastric pressure was noted in some animals when the volume of distension was 0.6 ml and this decreased further when the volume was increased in 0.1-ml increments up to 1.0 ml. To elicit stable responses, we Am J Physiol Regul Integr Comp Physiol 290: R1151–R1152, 2006; doi:10.1152/ajpregu.00584.2005. 0363-6119/06 $8.00 Copyright © 2006 the American Physiological Society http://www.ajpregu.org R1151 Downloaded from journals.physiology.org/journal/ajpregu (054.175.237.059) on December 6, 2021.