Afferent vagal pathways mediating respiratory reflexes evoked by ROS in the lungs of anesthetized rats

We investigated the afferent vagal pathways mediating respiratory reflexes evoked by reactive oxygen species (ROS) in the lungs of anesthetized rats. Spontaneous inhalation of 0.2% aerosolized H2O2 acutely evoked initial bradypnea followed by delayed tachypnea, which was frequently mixed with delayed augmented inspiration. The initial response was abolished after perivagal capsaicin treatment (PCT), but was prolonged during vagal cooling (VC) to 7°C; PCT and VC are known to differentially block the conduction of unmyelinated C and myelinated fibers, respectively. The delayed responses were eliminated during VC but emerged earlier after PCT. Vagotomy, catalase (an antioxidant for H2O2), dimethylthiourea (an antioxidant for · OH), or deferoxamine (an antioxidant for · OH) largely or totally suppressed these reflexive responses, whereas sham nerve treatment, heat-inactivated catalase, saline vehicle, or iron-saturated deferoxamine failed to do so. These results suggest that 1) the H2O2-evoked initial and delayed airway reflexes are antagonistic and may result from stimulation of lung C fibers and rapidly adapting receptors, respectively, and 2) the reflex effects of H2O2 are, in part, due to the action of · OH on these afferents.

The vagus is inhibitory of insulin secretion under fasting conditions

The involvement of the vagus in the insulin response during the early phase of absorption of a meal has been demonstrated recently. The extent of this vagal influence was investigated during fasting in an anesthetized porcine model. Portal and systemic insulin were evaluated together with glycemia during cooling and sectioning of both cervical vagal trunks in 12 splanchnicotomized or sham-operated pigs. In sham-operated animals, portal and systemic insulin were significantly and reversibly increased by cooling (173 and 123%, respectively). Portal insulin peaked 20 min after the onset of cooling but declined slowly while cooling was still activated. In contrast, systemic insulin was increased evenly along cooling. Section of the vagus was also associated with a portal and systemic insulin increase (144 and 117%) but to a lesser extent than cooling. In both treatments, portal and systemic insulin increases were either reduced (vagal cooling) or eliminated (vagal section) in splanchnicotomized animals. We conclude that the vagus exerts an inhibitory activity on interdigestive insulin secretion that is partly mediated by the splanchnic nerves.

Effect of hepatic denervation on the counterregulatory response to insulin-induced hypoglycemia in the dog

Our aim was to determine whether complete hepatic denervation would affect the hormonal response to insulin-induced hypoglycemia in dogs. Two weeks before study, dogs underwent either hepatic denervation (DN) or sham denervation (CONT). In addition, all dogs had hollow steel coils placed around their vagus nerves. The CONT dogs were used for a single study in which their coils were perfused with 37°C ethanol. The DN dogs were used for two studies in a random manner, one in which their coils were perfused with −20°C ethanol (DN + COOL) and one in which they were perfused with 37°C ethanol (DN). Insulin was infused to create hypoglycemia (51 ± 3 mg/dl). In response to hypoglycemia in CONT, glucagon, cortisol, epinephrine, norepinephrine, pancreatic polypeptide, glycerol, and hepatic glucose production increased significantly. DN alone had no inhibitory effect on any hormonal or metabolic counterregulatory response to hypoglycemia. Likewise, DN in combination with vagal cooling also had no inhibitory effect on any counterregulatory response except to reduce the arterial plasma pancreatic polypeptide response. These data suggest that afferent signaling from the liver is not required for the normal counterregulatory response to insulin-induced hypoglycemia.

Vagal esophageal receptors in anesthetized dogs: mechanical and chemical responsiveness

This study was performed to evaluate the characteristics of esophageal receptors in anesthetized and artificially ventilated dogs. The electrical activity of the esophageal afferents was recorded from the peripheral cut end of the cervical vagus nerve. A cuffed catheter was inserted into the esophagus at the level of the third tracheal ring and was used to establish the esophageal location of the endings. Most of the receptors were localized in the intrathoracic portion of the esophagus. The majority of the receptors studied (36 of 43) showed a slow adaptation to a maintained stretch of the esophageal wall. Vagal cooling blocked receptor activity at temperatures ranging from 3.5 to 25°C. Twenty-eight of 43 receptors, including 4 rapidly adapting endings (RAR), were challenged with saline, HCl + pepsin (HCl-P; pH 1) and distilled water (8 ml, 37°C). HCl-P solutions specifically stimulated only three receptors; saline or water did not. Five slowly adapting receptors and two RARs were also challenged with topically applied capsaicin; only one RAR was stimulated. To ascertain a possible effect of smooth muscle contraction, 17 receptors were tested with intravenous injections of ACh and/or asphyxia; only 4 were stimulated. These characteristics do not support an important reflexogenic role of the esophagus in response to chemical stimuli.

Erythromycin gastrokinetic activity is partially vagally mediated

Erythromycin overcomes postvagotomy gastroparesia in patients without a distal stomach and functional pylorus. We investigate the role of the vagus in gastric emptying increased by erythromycin, using a model that preserves the physiology of the distal stomach and pylorus. The effects of erythromycin lactobionate (10 mg/kg) on transpyloric flow pattern and pyloric resistance were evaluated during repetitive bilateral vagal cooling in anesthetized pigs. Vagal cooling during erythromycin infusion produced a marked decreased of pyloric outflow (23 ± 1.1 vs. 50 ± 2.6 ml/min) related to a reduced stroke volume of the flow pulses (7.8 ± 3.31 vs. 14.1 ± 2.44 ml). The amplitude and frequency of gastric and duodenal pressure events were unchanged or slightly reduced during vagal cooling. The smaller stroke volume of flow pulse was the consequence of increased pyloric resistance (6.2 ± 1.98 vs. 2.3 ± 0.21 mmHg ⋅ ml−1 ⋅ s), which is associated with changes in the temporal relationship between a pyloric pressure event and flow pulse. In conclusion, erythromycin activity on the pylorus requires the integrity of vagal pathways. Enhancement of gastric outflow by erythromycin is also modulated by the vagus, since pyloric resistance was able to overcome increased gastric motility.

Effects of vagal blockade on the counterregulatory response to insulin-induced hypoglycemia in the dog

Our aim was to determine whether vagal transmission is required for the hormonal response to insulin-induced hypoglycemia in 18-h-fasted conscious dogs. Hollow coils were placed around the vagus nerves, with animals under general anesthesia, 2 wk before an experiment. On the day of the study they were perfused with −15°C ethanol for the purpose of blocking vagal transmission, either coincident with the onset of insulin-induced hypoglycemia or after 2 h of established hypoglycemia. In a separate study the coils were perfused with 37°C ethanol in a sham cooling experiment. The following parameters were measured: heart rate, arterial plasma glucose, insulin, pancreatic polypeptide, glucagon, cortisol, epinephrine, norepinephrine, glycerol, free fatty acids, and endogenous glucose production. In response to insulin-induced hypoglycemia (42 mg/dl), plasma glucagon peaked at a level that was double the basal level, and plasma cortisol levels quadrupled. Plasma epinephrine and norepinephrine levels both rose considerably to 2,135 ± 314 and 537 ± 122 pg/ml, respectively, as did plasma glycerol (330 ± 60%) and endogenous glucose production (150 ± 20%). Plasma free fatty acids peaked at 150 ± 20% and then returned to basal levels by the end of the study. The hypoglycemia-induced changes were not different when vagal cooling was initiated after the prior establishment of hypoglycemia. Similarly, when vagal cooling occurred concurrently with the initiation of insulin-induced hypoglycemia (46 mg/dl), there were no significant differences in any of the parameters measured compared with the control. Thus vagal blockade did not prevent the effect on either the hormonal or metabolic responses to low blood sugar. Functioning vagal afferent nerves are not required for a normal response to insulin-induced hypoglycemia.