Regulation of beta-adrenergic receptor density in the non-innervated and denervated embryonic chick heart

Factors which regulate beta-adrenergic receptor density in non-innervated and denervated embryonic tissues have not been fully elucidated. In the present study, the effects of exposure to isoproterenol and propranolol on beta-adrenergic receptor density in the non-innervated (preneural) and partially innervated (neural) embryonic chick heart are examined. In addition, the effects of chemical and surgical sympathectomy on cardiac beta-adrenergic receptor density in the chick embryo are investigated. (125I)-pindolol was used as a receptor probe. The density of beta-adrenergic receptors in the embryonic chick heart peaks on incubation day 9 (664 fmols/mg protein) and then decreases by more than 80% by incubation day 19. Administration of propranolol or isoproterenol on incubation days 4 to 6 results in no change or a decrease (to 62% of control), respectively, in receptor density on incubation day 7. Administration of propranolol on incubation days 10 to 19 causes an increase (to 230% of control) in beta-adrenergic receptor density on day 20. Administration of isoproterenol on incubation days 10 to 16 results in a decrease (to 26% of control) in receptor density on day 17. Neither chemical sympathectomy, produced by administration of 6-hydroxydopamine, nor surgical sympathectomy, produced by removal of premigratory neural crest cells, significantly alters cardiac beta-adrenergic receptor density from control values. Administration of adrenergic drugs produces a greater change in beta-adrenergic receptor density after sympathetic innervation (day 10) than in preneural hearts. This indicates that sympathetic nerves influence the properties of beta-adrenergic receptors during embryonic development.     

Role of the autonomic nervous system in mediating the response to naloxone in canine hemorrhagic shock

When the opiate antagonist naloxone is administered to anesthetized dogs subjected to hemorrhagic shock, there is a transient decrease in heart rate and sustained increases in mean arterial pressure, maximum left ventricular dp/dt, and cardiac output. Surgical cardiac denervation and pharmacologic blockade of autonomic receptors were employed to investigate the mechanisms of these two responses. The transient bradycardia was prevented by beta-adrenergic receptor blockade or cardiac denervation. The sustained response was unaffected by cardiac denervation, attenuated by either alpha- or beta-adrenergic receptor blockade, and potentiated by cholinergic receptor blockade. Naloxone had no significant effect on plasma catecholamines. The sustained hemodynamic response to naloxone appears to have two components: there is an increase in parasympathetic stimulation which modestly attenuates the adrenergic component of the response. The adrenergic stimulation of the heart after naloxone administration appears to result from potentiation of existing adrenergic stimulation and not from increased sympathoadrenal discharge. These sustained sympathetic and parasympathetic responses appear to result from the action of naloxone at a myocardial site.     

Exercise unmasks autonomic dysfunction in swine with a recent myocardial infarction

OBJECTIVE: Severe congestive heart failure is associated with autonomic imbalance consisting of an increased sympathetic and decreased parasympathetic activity. In the present study, we investigated the influence of alterations in autonomic balance on cardiovascular function in 11 swine with left ventricular (LV) dysfunction produced by a 2- to 3-week-old myocardial infarction (MI). METHODS: Swine underwent permanent occlusion of the left circumflex coronary artery resulting in MI of the lateral LV wall. Autonomic activity was studied 2-3 weeks later using blockers of muscarinic (atropine), alpha-adrenergic (phentolamine) and beta-adrenergic (propranolol) receptors. RESULTS: Under resting conditions, parasympathetic and sympathetic control of the heart and coronary circulation were similar in MI and normal swine. In contrast, during exercise of MI compared to normal swine, (i) there was a more pronounced gradual inhibition of parasympathetic control of heart rate with increasing exercise intensity; (ii) circulating catecholamines increased excessively, resulting in an increased beta-adrenergic influence on heart rate, while (iii) the beta-adrenergic influence on global left ventricular contractility was decreased, reflecting a blunted left ventricular beta-adrenergic responsiveness. Furthermore, (iv) an alpha-adrenergic vasoconstrictor influence was absent in the anterior LV wall of both MI and normal swine, while (v) the beta-adrenergic vasodilator influence in the coronary circulation was not different between normal and MI swine, which, in conjunction with the elevated catecholamine levels during exercise, suggests a diminished beta-adrenergic responsiveness of coronary resistance vessels within remote non-infarcted myocardium in MI swine. CONCLUSIONS: Swine with a recent MI display autonomic dysfunction, which is characterized by a more pronounced inhibition of parasympathetic influence and an exaggerated increase in sympathetic drive during exercise, as well as reduced myocardial and coronary vascular beta-adrenergic responsiveness.     

Effects of autonomic nervous system on gastric damage by ethanol in the rat

To study whether or not the autonomic nervous system influences the defense mechanisms of the gastric mucosa, groups of Sprague-Dawley rats were given stimulants and inhibitors of the different components of the vagus and celiac nerves before administration of absolute or 70% w/v ethanol. The effects of vagotomy and sympathectomy on "adaptive cytoprotection" were studied, as were the effects of blocking the muscarinic receptors and stimulation of beta-adrenergic receptors. We found that: (1) cholinomimetic agents and norepinephrine make the damage caused by 70% ethanol worse; (2) atropine is the only agent that fully protects against absolute ethanol; (3) vagotomy and sympathectomy abolish the effects of atropine and adaptive cytoprotection; and (4) beta-adrenergic stimulation replaces conditions that allow adaptive cytoprotection and the protection by anticholinergics. These results suggest that two different reflexes are triggered by ethanol: when low concentrations are given, the beta-adrenergic-mediated effect is prevalent, with protection of the mucosa; when high concentrations are given, the cholinergic-mediated effect is prevalent with damage of the mucosa.     

Effect of different denervation procedures on catecholamines in the gut

Sympathectomy has been used to study the role of the sympathetic nervous system in the control of gastric acid secretion. Conflicting results may reflect differences in the sympathectomy procedures used. In a previous study we showed a reduction of catecholamines by more than 90% in the gut wall of the rat after surgical upper abdominal sympathectomy. The aim of the present investigation was to ascertain whether chemical sympathectomy was equally effective and whether total denervation, including combined chemical and surgical sympathectomy together with bilateral truncal vagotomy, would lower the catecholamine levels further. The results showed that chemical sympathectomy reduced noradrenaline levels in fundus (oxyntic) and antrum mucosa to levels similar to those after surgical sympathectomy (less than 5%), but the reduction was less pronounced in the muscle layer of the fundus and antrum and in the pancreas and spleen. Combined surgical and chemical sympathectomy did not reduce noradrenaline more effectively than surgical sympathectomy alone. Vagotomy reduced catecholamines in the stomach by about 50%; in extragastric tissues vagotomy was without effect. Total denervation, including combined surgical and chemical sympathectomy plus vagotomy, did not reduce noradrenaline levels more than surgical sympathectomy alone, suggesting that the proportion of adrenergic fibers that derive from the vagus is quantitatively insignificant but that the vagus exerts a local control of the sympathetic stores of gastric catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)     

Actin and myosin isoforms in aneural and malformed chick hearts

Although it is generally accepted that actin and myosin isoforms adapt to their functional requirements, the sequence of expression of these proteins in hearts developing abnormally is unknown. In the chick embryo it is possible to change various aspects of heart development without direct manipulation of the cardiovascular system, by removing various regions of the neural crest from early embryos. The neural crest provides both neural (sympathetic and parasympathetic) and ectomesenchymal components to the heart, and selective removal of various areas results in embryos with sympathetically aneural hearts, or persistent truncus arteriosus with or without parasympathetic denervation. Myosin isoform expression was studied in each of these types of hearts using an array of myosin antibodies specific for atrium, ventricle or the conduction system. Myosin expression in experimental hearts was found to follow the normal pattern of development using these antibodies. Actin expression was studied using cDNA probes for the 3' untranslated region of actin mRNA of the alpha-skeletal, alpha-cardiac and beta-actin isoforms. Using slot-blot hybridization analysis, the pattern of actin expression in atrium and ventricle was followed throughout the period of incubation in normal hearts. The pattern of actin expression was found to be abnormal in hearts which were sympathetically aneural and those which had persistent truncus arteriosus combined with parasympathetic denervation. ATPase activity was increased only in atria of hearts with persistent truncus arteriosus. It appears from these experiments that actin isoform expression is influenced in the chick heart by autonomic innervation.     

Partial cardiac sympathetic denervation after bilateral thoracic sympathectomy in humans

BACKGROUND: Upper thoracic sympathectomy is used to treat several disorders. Sympathetic nerve fibers emanating from thoracic ganglia innervate the heart. Whether unilateral or bilateral upper thoracic sympathectomy affects cardiac sympathetic innervation in humans in vivo has been unclear. OBJECTIVES: The purpose of this study was to assess whether thoracic sympathectomy decreases cardiac sympathetic innervation, as indicated by positron emission tomographic scanning after intravenous injection of the sympathoneural imaging agent 6-[18F]fluorodopamine. METHODS: Nine patients with previous upper thoracic sympathectomies (four right-sided, one left-sided, four bilateral) underwent thoracic 6-[18F]fluorodopamine scanning between 1 and 2 hours after injection of the imaging agent. In each case, a low rate of entry of norepinephrine into the arm venous drainage (norepinephrine spillover) verified upper limb sympathectomy. Data were compared with those from the interventricular septum of patients with cardiac sympathetic denervation associated with pure autonomic failure and from normal volunteers. RESULTS: All four patients with bilateral sympathectomy had low septal myocardial 6-[18F]fluorodopamine-derived radioactivity (2,673 +/- 92 nCi-kg/cc-mCi at an average of 89 minutes after injection) compared with normal volunteers (3,634 +/- 311 nCi-kg/cc-mCi at 83 minutes, N = 22, P = .007) and higher radioactivity than in patients with pure autonomic failure (1,320 +/- 300 nCi-kg/cc-mCi at 83 minutes, N = 7, P = .003). Patients with unilateral sympathectomy had normal 6-[18F]fluorodopamine-derived radioactivity (3,971 +/- 337 nCi-kg/cc-mCi at 87 minutes). CONCLUSIONS: Bilateral upper thoracic sympathectomy partly decreases cardiac sympathetic innervation density.     

Experimental study of the pathogenesis of acute acalculous cholecystitis: Role of autonomic denervation

This study was undertaken to elucidate the role of autonomic denervation in the pathogenesis of acute acalculous cholecystitis. In Experiment I, the gallbladder was denervated by performing either celiac neurotomy (sympathetic denervation) or truncal vagotomy (parasympathetic denervation), or both, in dogs. In Experiment II, 45-min ischemia and 90-min reperfusion of the gallbladder with or without autonomic denervation were performed by simultaneously occluding the middle hepatic artery and superior mesenteric vein. Celiac neurotomy, and truncal vagotomy, or both, did not cause cholecystitis. Sympathetic denervation, however, decreased the amount of mucin in the gallbladder mucosa and parasympathetic denervation caused reduction of the tissue blood flow, as well as the accumulation of lipid peroxide and xanthine oxidase in the gallbladder mucosa. These changes were most remarkable 1–2 weeks after denervation and were alleviated 4 weeks after denervation. Ischemia-reperfusion 2 weeks after denervation caused more severe cholecystitis than ischemia-reperfusion alone. The most severe inflammation developed in animals that received both celiac neurotomy and truncal vagotomy. These results suggest that autonomic denervation alone does not induce acute cholecystitis, but that it plays an important role in the progression of the inflammatory process in ischemia-reperfusion injury.     

Cardiac ion channel expression and regulation: the role of innervation

The expression and function of numerous cardiac ion channels change with development and disease. Whereas multiple regulatory processes and molecular mechanisms are certainly involved, one factor, sympathetic innervation, contributes to many of the developmental changes and is suggested to play a role in pathology. The onset of cardiac sympathetic innervation of the mammalian ventricle during early post-natal life has been associated with functional alterations in several ionic currents, including Na(+), L-type Ca(2+), pacemaker, inward rectifier and transient outward K(+) currents. The neural signaling molecule is not the same in each case, with evidence pointing to contributions from sustained activation of myocardial neuropeptide Y receptors, alpha-adrenergic receptors and beta-adrenergic receptors, as well as additional, but as yet unidentified, targets. Knowledge of the mechanisms by which innervation regulates ion channel expression and function during normal development may aid efforts to reverse remodel the diseased heart and to target pharmacologic agents to remodeled channels.     

The vagus, the duodenal brake, and gastric emptying.

It has been suggested that an intact vagal supply is essential for the normal function of the recptors in the duodenum and proximal small bowel, which influence the rate of gastric emptying. This paper reports the effect of vagal denervation on gastric emptying and also examines the site and mode of action of receptors in the proximal small bowel.It has been demonstrated in the dog that most, if not all, the receptors controlling gastric emptying lie in the proximal 50 cm of the small bowel. Following truncal vagotomy the emptying time of each instillation increased significantly and the differential rate of emptying of different instillations remained unchanged. The proximal 50 cm of small bowel was capable to differentiating between different instillates even after selective extragastric vagotomy, in which the duodenum was vagally denervated and, therefore, duodenal braking receptors function independently of vagal innervation.     

Effects of autonomic denervation on canine exocrine pancreatic secretion and blood flow

The effect of autonomic denervation on the exocrine pancreatic secretion and blood flow was studied in a group of dogs. Pancreatic secretion was collected and analyzed for volume and bicarbonate by direct cannulation of the main papilla through a duodenotomy prior to and following truncal vagotomy and celiac plexus denervation. Pancreatic blood flow was determined by the radioisotope distribution method (141Ce). Truncal vagotomy causes a reduction in pancreatic secretion of volume and bicarbonate by 25-30%, while celiac denervation caused a reduction of 70% in the secretion. The mean baseline pancreatic blood flow was 0.5 ml/g pancreas/min. Truncal vagotomy did not cause any significant flow changes, while celiac denervation caused a significant increase in blood flow of 350% (to 1.75 ml/g/min). These results suggest that both the parasympathetic and the sympathetic system affect pancreatic secretion independently of their effect upon pancreatic blood flow.     

Primary structure of rat cardiac beta-adrenergic and muscarinic cholinergic receptors obtained by automated DNA sequence analysis: further evidence for a multigene family.

Two cDNA clones, lambda RHM-MF and lambda RHB-DAR, encoding the muscarinic cholinergic receptor and the beta-adrenergic receptor, respectively, have been isolated from a rat heart cDNA library. The cDNA clones were characterized by restriction mapping and automated DNA sequence analysis utilizing fluorescent dye primers. The rat heart muscarinic receptor consists of 466 amino acids and has a calculated molecular weight of 51,543. The rat heart beta-adrenergic receptor consists of 418 amino acids and has a calculated molecular weight of 46,890. The two cardiac receptors have substantial amino acid homology (27.2% identity, 50.6% with favored substitutions). The rat cardiac beta receptor has 88.0% homology (92.5% with favored substitutions) with the human brain beta receptor and the rat cardiac muscarinic receptor has 94.6% homology (97.6% with favored substitutions) with the porcine cardiac muscarinic receptor. The muscarinic cholinergic and beta-adrenergic receptors appear to be as conserved as hemoglobin and cytochrome c but less conserved than histones and are clearly members of a multigene family. These data support our hypothesis, based upon biochemical and immunological evidence, that suggests considerable structural homology and evolutionary conservation between adrenergic and muscarinic cholinergic receptors. To our knowledge, this is the first report utilizing automated DNA sequence analysis to determine the structure of a gene.     

Protective effect of vagal stimulation on reperfusion arrhythmias in cats

The role of the autonomic nervous system in modulating reperfusion arrhythmias is still unclear. Experiments with sympathetic denervation or alpha- and beta-adrenergic blocking agents have provided mixed results, while the effect of parasympathetic activation has not been investigated extensively. The effect of bilateral vagotomy and of vagal stimulation was studied, with and without attendant bradycardia, on the incidence of reperfusion arrhythmias in alpha-chloralose anesthetized cats. The left anterior descending coronary artery was occluded for 20 minutes, followed by reperfusion in 105 animals. The incidence and severity of reperfusion arrhythmias was compared in 1) neurally intact animals (heart rate 208 +/- 24 beats/min), 2) animals with acute bilateral vagotomy (heart rate 233 +/- 25 beats/min), 3) animals with vagal stimulation adjusted to maintain heart rate at 90-100 beats/min, and 4) animals with vagal stimulation + ventricular pacing to maintain heart rate at prestimulation values. All the neurally intact and vagotomized animals developed complex reperfusion arrhythmias, but these arrhythmias occurred in only 60 and 72%, respectively, of the animals with vagal stimulation and vagal stimulation + pacing (p less than 0.005 vs. neurally intact and p less than 0.02 vs. vagotomy). The incidence of ventricular fibrillation was similar in neurally intact (62%) and vagotomized (58%) animals; it was strikingly lower (7%, p less than 0.01) in animals with vagal stimulation when heart rate was allowed to decrease, and it was 48% when heart rate was kept constant during vagal stimulation. A selective protection from sustained (greater than 30 seconds duration) ventricular tachycardia was observed in animals with vagal stimulation independent of heart rate changes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Advanced autonomic cardiovascular denervation of diabetic etiology. Presentation of a case

"Functional" total cardiac denervation due to diabetic autonomic neuropathy, is relatively rare. Sympathetic and parasympathetic fibers differ in the frequency with which they are damaged, with preference of parasympathetic abnormality. We report a diabetic patient who presented cardiac denervation with fixed heart rate at rest (95 beats for minute), severe orthostatic hypotension and cardiovascular abnormalities such as absence of reactions to physiological and pharmacological stimuli, sympathetic and parasympathetic. To the best of our knowledge our patient is the third such case in the literature.     

Effects of autonomic denervation on canine exocrine pancreatic secretion and blood flow

Summary The effect of autonomic denervation on the exocrine pancreatic secretion and blood flow was studied in a group of dogs. Pancreatic secretion was collected and analyzed for volume and bicarbonate by direct cannulation of the main papilla through a duodenotomy prior to and following truncal vagotomy and celiac plexus denervation. Pancreatic blood flow was determined by the radioisotope distribution method (¹⁴¹Ce). Truncal vagotomy causes a reduction in pancreatic secretion of volume and bicarbonate by 25–30%, while celiac denervation caused a reduction of 70% in the secretion. The mean baseline pancreatic blood flow was 0.5 ml/g pancreas/min. Truncal vagotomy did not cause any significant flow changes, while celiac denervation caused a significant increase in blood flow of 350% (to 1.75 ml/g/min). These results suggest that both the parasympathetic and the sympathetic system affect pancreatic secretion independently of their effect upon pancreatic blood flow.     

Endogenous tyrosine hydroxylase activity in the developing chick heart: a possible source of extraneuronal catecholamines

The source of catecholamines in the developing chick heart was investigated by using catecholamine assays and tyrosine hydroxylase assays on hearts from normal and chemically-sympathectomized chick embryos. A biochemical index of sympathetic nerve development in the heart was obtained by monitoring the ability of sympathetic nerves in the atria to take up [3H]-norepinephrine in vitro. Specific neuronal uptake of [3H]-norepinephrine in atria was first detected on incubation day 11 and increased throughout the incubation period. High performance liquid chromatography with electrochemical detection was used to measure the norepinephrine concentration and content of embryonic hearts. The cardiac norepinephrine concentration fluctuated throughout the incubation period but was particularly low (0.01 +/- 0.005 ng/mg wet wt) on incubation days 10 to 13, coincident with the arrival of sympathetic nerves in the heart. The highest norepinephrine concentration was measured on incubation day 7 (2.09 +/- 0.50 ng/mg wet wt) prior to the arrival of sympathetic nerves in the heart. Sympathetic nerve axotomy produced by chronic treatment with 6-hydroxydopamine reduced [3H]-norepinephrine uptake in atria and norepinephrine concentration in whole hearts on incubation day 20 to 33 and 47% of control, respectively. Tyrosine hydroxylase activity was detected in normal hearts on incubation day 7, 3 to 4 days before the heart is innervated by sympathetic nerves. Tyrosine hydroxylase activity persisted in the heart on incubation day 20, despite treatment with 6-hydroxydopamine on incubation days 13 to 19. The tyrosine hydroxylase activity in 6-hydroxydopamine lesioned hearts was not significantly different from saline-treated controls. This data indicates that tyrosine hydroxylase activity is present in the immature chick heart prior to the arrival of sympathetic innervation and following chemical sympathectomy; hence, an extraneuronal source of tyrosine hydroxylase, the rate limiting enzyme for catecholamine biosynthesis, exists in the embryonic chick heart.     

Differential control of adrenal and renal sympathetic nerve activity during hemorrhagic hypotension in rats

The reflex mechanisms that produce the neurocirculatory adjustments to hemorrhagic hypotension are incompletely understood. The goal of this study was to determine if hemorrhagic hypotension in rats produces differential effects on sympathetic outflow to the adrenal gland and kidney and if the two sympathetic nerve responses are governed by different reflex mechanisms. We performed simultaneous multifiber recordings of adrenal and renal sympathetic nerve activity (SNA) during 8 minutes of sustained hemorrhagic hypotension to a mean arterial pressure of 50 mm Hg in chloralose-anesthetized Sprague-Dawley rats with a) baroreceptors intact, b) cervical vagotomy, c) sinoaortic baroreceptor denervation, and d) combined vagotomy plus sinoaortic denervation. During hemorrhagic hypotension in rats with intact baroreceptors, renal SNA decreased by 31 +/- 10% (mean +/- SEM, p less than 0.05 vs. control) and heart rate decreased from 384 +/- 13 to 365 +/- 16 beats per minute (p less than 0.05), but adrenal SNA increased by 69 +/- 10% over control (p less than 0.05). The decreases in renal SNA and heart rate were reversed by cervical vagotomy but not by atropine, which indicates vagal afferent mediation. In contrast, the increases in adrenal SNA during hemorrhage were not affected by vagotomy alone or by sinoaortic denervation alone but were markedly attenuated by combined sinoaortic denervation and vagotomy, which indicates redundancy in the baroreflex control of adrenal SNA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sympathetic innervation alters growth and intrinsic heart rate of fetal rat atria maturing in oculo

The influence of sympathetic innervation on the growth and intrinsic rate of beating established by fetal rat heart was studied by culturing fetal atrial tissue in sympathetically innervated and denervated anterior eye chambers of adult Sprague-Dawley rats. One anterior eye chamber in each host rat was sympathetically denervated by removing the ipsilateral superior cervical ganglion. In oculo, atrial grafts were vascularized by blood vessels sprouting from the iris and innervated by sympathetic and parasympathetic fibers from the ground plexus of the iris. Innervation was assessed by light-activated efferent nerve stimulation to the grafts that changed their rates of beating. The norepinephrine contents of 16 atria cultured for 2.5 months in sympathetically innervated and denervated eye chambers were 5.7 +/- 1.1 ng/implant vs. 0.2 +/- 0.07 ng/implant (mean +/- SEM), indicating permanent sympathetic denervation of the anterior eye chamber and the implanted atria. By 8 weeks in oculo, atria maturing in sympathetically innervated anterior eye chambers were 86% larger than those in denervated eye chambers (2.22 +/- 0.29 vs. 1.19 +/- 0.13 mm2); the weight of innervated transplants was over 3 times that of noninnervated grafts (2.35 +/- 0.75 vs. 0.76 +/- 0.21 mg). After implanted atria had ceased growing rapidly (2.5 months in oculo), bipolar electrodes were implanted adjacent to the cornea to record impulses from atrial grafts while host rats were unanesthetized. The dark-adapted baseline heart rates of sympathetically innervated and noninnervated atria were virtually identical (289 vs. 290 bpm). Graft intrinsic heart rate was estimated by combined beta-adrenergic and muscarinic receptor blockade with atenolol (1.0 mg/kg) and methylatropine (10 micrograms/kg). Sympathetically innervated transplants had lower intrinsic heart rates than noninnervated atria (134 +/- 25 vs. 213 +/- 12 bpm). These data suggest that sympathetic innervation of the developing heart influences both growth and intrinsic rate of beating.     

Pancreatic polypeptide response to a meal before and after cutting the extrinsic nerves of the upper gastrointestinal tract and the pancreas in the dog

The role of the sympathetic and parasympathetic innervation in the release of pancreatic polypeptide (PP) basally and in response to a meal was studied after stepwise extrinsic denervation of the pancreas and the upper gastrointestinal tract in conscious dogs with gastric fistulae. One set of seven dogs was fed a meat meal (35 g/kg body weight) before and after truncal vagotomy and after truncal vagotomy plus celiac and superior mesenteric ganglionectomy, ie, extrinsic denervation of the pancreas and the upper gastrointestinal tract. In another set of six dogs, only ganglionectomy was performed. Experiments were repeated in the presence of atropine (50 g/kg body weight, given as an intravenous bolus 60 min prior to the meal). Truncal vagotomy significantly (P<0.05) reduced the postprandial 120-min integrated plasma PP response (IPPPR) by 84% as compared to the prevagotomy response. Before truncal vagotomy, atropine significantly reduced the IPPPR by 57%. After truncal vagotomy, atropine completely abolished the residual PP response. Additional celiac and superior mesenteric ganglionectomy did not alter the IPPPR already reduced by truncal vagotomy. With the vagus nerves intact, ganglionectomy alone had no effect on the IPPPR whether or not atropine was given. These findings indicate that (1) the splanchnic nerves do not play a significant role in postprandial PP release and (2) that the vagus nerves are important mediators of the response to a meal. The effect of atropine on postprandial PP release after truncal vagotomy may be due to interruption of short enteropancreatic reflexes, suppression of the intrinsic cholinergic activity of the pancreas, or inhibition of hormonally induced PP release.     

Changes in cholinergic parameters associated with failure of conotruncal septation in embryonic chick hearts after neural crest ablation

Cells from the neural crest over occipital somites migrate to the heart, where they give rise to parasympathetic postganglionic neurons as well as ectomesenchymal elements which contribute to conotruncal septation. With a microcautery needle, the neural crest over occipital somites was ablated bilaterally in chicken embryos at an early stage of development. Histological examination on incubation day 15 revealed conotruncal malformations, involving malformation or absence of the conotruncal septum in all embryos. Two peaks of embryo mortality were observed. One peak (incubation days 6-8) occurred at the same time as conotruncal septal closure; the second peak (incubation days 11-13) was concurrent with the onset of functional parasympathetic innervation. A disruption of parasympathetic innervation was indicated by: (1) a decrease in acetylcholinesterase staining, (2) a decrease (27%) in the number of ganglion cells in the conotruncus, (3) decreases in the acetylcholine content of atrium (31%) and ventricle (39%), and (4) a decrease (21%) in muscarinic acetylcholine receptor density on incubation day 15. Radiolabeled ligand-binding studies revealed no change in the affinity of cardiac muscarinic receptors for [3H]methylscopolamine (KD = 0.17-0.21 nM). Agonist-binding affinity and sensitivity to guanine nucleotides were similarly unaffected. The reasons for the limited extent of the parasympathetic lesion are unclear, but may involve recruitment of precursor cells from other regions of the neural crest, partial regeneration of the neural crest following surgical removal, or an alteration in the contribution of incoming sympathetic or preganglionic parasympathetic elements. No such plasticity was associated with neural crest contributions to the structural development of the conotruncus. Malformations were observed in all lesioned embryos.