Effect of vagotomy and thoracic sympathectomy on responses of the monkey to water immersion

Cardiopulmonary stretch receptors have been implicated as part of a reflex mechanism linking changes in blood volume to changes in renal excretion. Experiments were performed to determine whether total denervation of these receptors by combined cervical vagotomy and thoracic sympathectomy affects the renal responses of the monkey to head-out water immersion, a maneuver that translocates blood to the thorax and elicits an increase in renal salt and water excretion. Macaca fascicularis monkeys first underwent chronic bilateral thoracic sympathectomy or sham denervation performed in two stages a week apart. One to two weeks later, they were anesthetized with pentobarbital sodium, and the sympathectomized animals underwent bilateral cervical vagotomy. Control renal function did not differ between the two groups. Immersion of 90-min duration increased central venous and mean arterial pressures by similar amounts in both groups, but heart rate increased only in the sham-denervated animals. Denervation did not affect the magnitudes or delay the times of onset of the increases in urine flow, absolute and fractional sodium excretion, and osmolar and free water clearances occurring with immersion. These results demonstrate that in the anesthetized monkey cardiopulmonary receptors are not necessary for eliciting the renal responses to immersion.     

Plasma vasopressin and atrial natriuretic factor in response to blood volume changes in the anaesthetized rabbit

The influence of aortic baroreceptors and vagal afferent nerves on the release of immunoreactive vasopressin (iVP) and immunoreactive atrial natriuretic factor (iANF) was examined in anaesthetized rabbits. Changes in plasma concentrations of iVP and iANF, heart rate, mean arterial pressure, and right atrial pressure were measured in response to blood volume changes (+20, +10, -10, -20%). Carotid sinus pressure was maintained at 100 mmHg (1 mmHg = 133.3 Pa), and blood volume changes were performed before and after bilateral vagotomy (VNX) in all experiments. Two experimental groups were studied: rabbits with aortic depressor nerves intact (ADNI) and those with aortic depressor nerves sectioned (ADNX). Mean arterial and right atrial pressures decreased during haemorrhage and increased in response to volume expansion. Plasma iVP concentrations increased with haemorrhage and decreased with volume expansion in the ADNI group. Plasma iANF, however, decreased with haemorrhage and increased during volume expansion in both ADNI and ADNX groups. Vagotomy caused an increase in baseline plasma iANF in the ADNX group. The responses of iANF to blood volume changes were augmented after VNX and ADNX. The results show that neither the aortic baroreceptor nor the vagal afferent input are needed for the iANF response to changes in blood volume, over the range of +/- 20%. In contrast, intact aortic baroreceptors are essential for changes in circulating iVP in this preparation.     

Ultrastructure of the area postrema of the monkey, Macaca fascicularis

The area postrema of the monkey, Macaca fascicularis, were a pair of oval organs at the caudal end of the floor of fourth ventricle. Their ependymal lining was covered by well-developed microvilli with occasional overlying supraependymal cells. Two types of lining cells were present: pyramidad- and flattened cells. The pyramidal cell showed a long extending basal process resting on the underlying blood vessels. In transmission electron microscopy, the organ showed numerous fenestrated sinusoids characterized by a distinct perivascular space containing mast cells, macrophages and collagen fibrils. The parenchyma of the organ was composed of neurons and glial elements. Only one type of neuron ranging from 9.5 to 15 microns could be distinguished. The neurons contained an indented nucleus surrounded by organelle rich cytoplasm. The soma of the neuron was enclosed by glial element resembling astrocyte. The glial processes terminated on the blood vessel where they were "tunnelled" by a variable number of nerve fibres some of which gained a direct access to the external basal lamina of the perivascular space. Synapses in the neuropil predominantly of the axodendritic variety were observed. Axon terminals containing round agranular vesicles were seen to make synaptic contacts with the neuronal soma. No structural changes were observed in the area postrema following bilateral cervical vagotomy. However, degenerating axon terminals were observed in the subpostremal zone 7, 14 and 21 days after vagotomy suggesting a direct afferent projection into this region.     

Ultrastructure of interstitial cells of Cajal at the gastro-oesophageal junction of the monkey (Macaca fascicularis)

The ultrastructure of the interstitial cells of Cajal (ICC) in the oesophagus of the monkey resembled that described in the oesophagus of other mammalian species but differed in their paucity and almost lack of smooth endoplasmic reticulum, caveolae and filaments. The plasmalemma of the ICC was in close contact (20- to 30-nm gaps) with that of smooth muscle cells. This may occasionally take the form of a desmosome, but gap junctions have not been observed. Vesiculated axon profiles, containing large granular or agranular vesicles were in close contact (20- to 30-nm gaps) with the plasmalemma of ICC. In a few vesiculated profiles a presynaptic density could be recognized. The intercalation of the ICC between the vesiculated axon profiles and the smooth muscle cells suggest a role in oesophageal motility. Between 3 and 21 days following bilateral vagotomy some ICC showed regressive changes such as increased electron density and shrinkage of the cytoplasm, crowding of the organelles and dissolution of the nuclear chromatin material. Axon profiles in the vicinity of the affected ICC contained glycogen granules suggesting injury. In late stages, the number of ICC and smooth muscle contacts was reduced. The results suggest that the vagus nerves exert a trophic influence on the ICC and that the intercellular relationships between ICC and smooth muscle cells possess a degree of plasticity. It is tentatively suggested that these vagal effects may be mediated via the oesophageal myenteric ganglia.     

迷走神经在心率变异性中的作用

采用功率谱和近似熵 (approximateentropy ,ApEn)的方法 ,分析清醒家兔在双侧迷走神经保留 ,右、左侧迷走神经切断以及双侧迷走神经同时切断时心搏间期 (RRI)的变化。结果显示 :双侧迷走神经保留时功率谱中高频功率 (HF)、低频功率 (LF)及ApEn值均高于双侧及单侧迷走神经切断时 (P <0 0 5 ) ,LF/HF比值最小 ;切断单侧迷走神经 ,ApEn变小 ,LF/HF比值在右侧迷走神经切断时增大 ,而切断左侧迷走时LF/HF比值无明显变化 ;双侧迷走神经切断后LF/HF比值最大 ,ApEn最低。结果表明 :心率变异主要由迷走神经调节 ,右侧迷走神经起主要作用 ;传统心率变异性测量方法与非线性方法所得结果一致     

Changes in rat liver mitochondria under conditions of bilateral subdiaphramatic vagotomy]

A study was made of the changes in the mitochondria of the rat liver under conditions of bilateral subphrenic vagotomy. Two stages in the dynamics of the response of the mitochondrial apparatus to denervation were distingished. During the first stage (0.5-3 days after vagotomy) there occurred reversible functional disturbances of the mitochondria caused by the postoperative stress. The second stage (7 to 60 days after the denervation) was charaterized by more marked structural-functional changes having a number od common features with those seen in hypoxia and being result of vagotomy proper.     

不同生理状态对大鼠右心耳肌细胞特殊颗粒的影响──形态学和计量学研究

本文通过电镜观察和立体计量学方法,研究迷走神经和肾上腺素对ＳＤ大鼠右心耳肌细胞特殊颗粒（ＳＧ）的影响。结果是迷走神经切除组ＳＧ的体密度（ＶＶ）、颗粒平均直径（Ｄ）明显小于对照组（Ｐ＜０．００１）,肾上腺素组ＳＧ的ＶＶ、Ｄ、数密度（Ｎｖ）也明显小于相应对照组（Ｐ＜０．００１）。结果提示迷走神经对心钠素的释放是抑制作用,肾上腺素对心钠素的释放是促进作用。本研究还为ＳＧ的产生与分型,心钠素的多种释放方式提供了形态学资料。     

Stimulation by volume expansion of atrial natriuretic peptide release from perfused rat heart

The release of immunoreactive (ir-) rat atrial natriuretic peptide (rANP) with volume expansion in in situ retrograde perfused rat heart was examined. The volume expansion induced by the infusion of the perfusion medium into the right atrium increased the mean right atrial pressure and the ir-rANP release without changing the rate of the heart beat. There was a significant correlation between the peak values of ir-rANP release and those of mean atrial pressure. The bilateral cervical vagotomy did not effect the ir-rANP release induced by the volume expansion. Therefore, it is highly likely that the stimulatory effect of volume expansion on rANP release is due to, at least in part, the atrial distension accompanied by an increase in mean atrial pressure, not involving a vagal system.     

Effects of expansion of blood volume and bilateral vagotomy on specific heart granules and release of atrial natriuretic peptide in the rat

Summary There was no statistically significant difference in basal concentrations of immunoreactive atrial natriuretic peptide (ANP), as assessed by radioimmunoassay, between right and left atrial muscle of control rats; similarly, stereological analysis showed no statistically significant difference in the fractional volume of myocytes occupied by specific heart granules, or in numerical density of granules, between right and left atria. Nevertheless, correlated radioimmunoassay and ultrastructural investigations showed that the major source of elevated plasma levels of ANP after expansion of blood volume was the right atrium. Substantial expansion of blood volume caused an increase in the proportion of peripherally located granules in myocytes of both atria, but reduction in the number of granules and in the concentration and total content of ANP occurred in the right atrium only. Bilateral cervical vagotomy also caused a statistically significant elevation of plasma ANP concentration, accompanied by a statistically significant reciprocal reduction in right atrial ANP content; no statistically significant change occurred in left atrial ANP. When blood volume was expanded after bilateral vagotomy, there was a further statistically significant increase in plasma ANP concentration; this was accompanied by further reduction in right atrial ANP and, moreover, the combined manoeuvre also elicited a statistically significant reduction of ANP in the left atrium. Ultrastructural studies confirmed that, under these conditions, myocytes in both atria showed a marked depletion of specific heart granules.     

在大鼠牵拉心房和急性扩张血容量所致的肾效应

在28只麻醉大鼠,观察了牵拉心房和急性扩容时的肾效应。用5—7g的砝码牵拉大鼠右心房30min(n=6)时,尿量、尿钠和尿钾分别增加98％、127％和59％;牵拉左心房(n=4)所致的肾效应与牵拉右心房的基本相同。切断双侧迷走神经后,牵拉右心房的肾效应无明显改变。在切断迷走神经的大鼠,观察了双线结扎右心耳对急性扩容后肾效应的影响。急性扩容在假手术大鼠引起明显的利尿、钠尿和钾尿效应(P<0.01);而结扎右心耳的大鼠,钠尿效应约为假手术大鼠的一半,但尿量和尿钾排泄量与假手术组无明显异差。上述肾效应不受切断迷走神经的影响,因此不是通过容量感受性反射引起的。根据以上结果,我们推测,牵拉心房或急性扩容引起的尿量、尿铜和尿钾的增多,可能是心房钠尿因子释放增多所致,而结扎右心耳则导致释放入血流的心房钠尿因子减少。     

Thromboxane A2-induced arrhythmias in the anesthetized rabbit

Experiments were conducted in the anesthetized rabbit to investigate mechanisms for arrhythmias that occur after left atrial injection of the thromboxane A(2) (TxA(2)) mimetic U-46619. Arrhythmias were primarily of ventricular origin, dose dependent in frequency, and TxA(2) receptor mediated. The response was receptor specific since arrhythmias were absent after pretreatment with a specific TxA(2) receptor antagonist (SQ-29548) and did not occur in response to another prostaglandin, PGF(2alpha). Alterations in coronary blood flow were unlikely the cause of these arrhythmias because coronary blood flow (as measured with fluorescent microspheres) was unchanged after U-46619, and there were no observable changes in the ECG-ST segment. In addition, arrhythmias did not occur after administration of another vasoconstrictor (phenylephrine). The potential involvement of autonomic cardiac efferent nerves in these arrhythmias was also investigated because TxA(2) has been shown to stimulate peripheral nerves. Pretreatment of animals with the beta-adrenergic receptor antagonist propranolol did not reduce the frequency of these arrhythmias. Pretreatment with atropine or bilateral vagotomy resulted in an increased frequency of arrhythmias, suggesting that parasympathetic nerves may actually inhibit the arrhythmogenic activity of TxA(2). These experiments demonstrate that left atrial injection of U-46619 elicits arrhythmias via a mechanism independent of a significant reduction in coronary blood flow or activation of the autonomic nervous system. It is possible that TxA(2) may have a direct effect on the electrical activity of the heart in vivo, which provides significant implications for cardiac events where TxA(2) is increased, e.g., after myocardial ischemia or administration of cyclooxygenase-2 inhibitors.     

Quantitative Changes of Amino Acid Distributions in the Rat Vestibular Nuclear Complex After Unilateral Vestibular Ganglionectomy

Abstract: Changes of amino acid concentrations in the vestibular nuclear complex (VNC) during lesion-induced vestibular compensation were studied in rats after unilateral vestibular ganglionectomy. Distributions of 12 amino acids within the VNC were measured at 2, 4, 7, and 30 days after surgery, using microdissection of freeze-dried brain sections and HPLC. Glutamate decreased on the lesioned side in nearly all VNC regions. Changes were fully developed 2 days after lesion and persisted through 30 days. In some regions, glutamate decreased also on the unlesioned side, especially at longer survival times, so that bilateral asymmetries became reduced. Aspartate changes were similar to those of glutamate on either side. Lesion-induced glutamine asymmetry was usually opposite to that of glutamate. Although GABA concentration decreased at early survival times, it recovered at later times and sometimes increased in dorsal parts of lateral and medial nuclei. Taurine changes were similar to those of GABA in most regions. Glycine change was primarily limited to a bilateral decrease in the dorsal part of the lateral vestibular nucleus. Concentrations of other amino acids were much lower, but some showed postlesion changes.     

Centrally applied atrial natriuretic factor diminishes bile secretion in the rat.

Little is known about the role of centrally applied peptides in the regulation of bile secretion. We previously reported that the intravenous injection of atrial natriuretic factor (ANF) reduces bile acid dependent flow without affecting portal venous pressure in the rat. In the present work, we studied the effects of centrally applied ANF on bile secretion and the possible pathways involved. Rats were cannulated in the brain lateral ventricle for the administration of 1, 10 and 100 ng/microl ANF. After 1 week, the common bile duct was cannulated and bile samples were collected every 15 min for 60 min after the administration of ANF. The excretion rate of various biliary components was assessed. Bile secretion experiments were also performed after bilateral truncal vagotomy or atropine administration to evaluate the participation of a vagal pathway. In addition, the role of the sympathetic system was addressed by combined administration of propranolol and phentolamine. Centrally applied ANF did not modify blood pressure but diminished bile flow and bile acid output. It also reduced sodium and potassium secretion but did not modify protein or phospholipid excretion. Neither bilateral truncal vagotomy nor atropine administration abolished ANF response. Furthermore, combined administration of adrenergic antagonists did not alter ANF inhibitory effect on bile flow. In conclusion, centrally applied ANF reduced bile acid dependent flow not through a vagal or adrenergic pathway in the rat, suggesting the involvement of a peptidergic pathway.     

二十二碳六烯酸对心房颤动大鼠心房肌生理改变及双孔钾通道TASK-1蛋白表达的影响

目的：探讨二十二碳六烯酸（DHA）对大鼠心房颤动（AF）模型心房肌生理特性的影响及相关机制研究。方法：80只乙酰胆碱-氯化钙混合液敏感的SD大鼠分为对照组（CTL组）、DHA处理组（DHA组）、房颤组（AF组）和房颤+DHA处理组（DHA+AF组）,观察房颤持续时间;采用全细胞膜片钳技术记录大鼠心房肌细胞动作电位时程（APD）和双孔钾通道TASK-1电流,Western blot测定大鼠心房组织TASK-1蛋白表达。结果：大鼠尾静脉注射乙酰胆碱-氯化钙混合液后,房颤持续时间随实验天数增加而逐渐延长,DHA干预缩短房颤持续时间。与CTL组相比,AF组大鼠心房肌细胞复极50%时的动作电位时程（APD₅₀）和复极90%时的动作电位时程（APD₉₀）明显缩短,心房肌细胞TASK-1电流密度升高,蛋白表达升高（P<0.05）。与AF组相比,DHA+AF组大鼠心房肌细胞APD₅₀和APD₉₀明显延长,TASK-1电流密度和蛋白表达降低（P<0.05）。结论：DHA具有延长房颤大鼠心房肌细胞APD的作用,可能与其下调心房肌TASK-1蛋白的表达从而降低心房肌细胞TASK-1电流密度有关。     

Time course of release of atrial natriuretic peptide in the anaesthetized dog

In 12 chloralose anaesthetized dogs plasma concentration of immunoreactive atrial natriuretic peptide (IR-ANP) was measured using a radioimmunoassay. Plasma IR-ANP was 74 +/- 4.8 pg/mL (mean +/- SE) and increased by 39 +/- 4.1 pg/mL when left atrial pressure was increased by 10 cm H2O during partial mitral obstruction. Observation of the time course of the changes in IR-ANP during atrial distension showed that IR-ANP was increased within 2 min of atrial distension and declined after atrial distension, with a half-time of 4.5 min. The time course of the changes in IR-ANP was unaffected by vagotomy or administration of atenolol. Maximum electrical stimulation of the right ansa subclavia failed to produce any change in IR-ANP. IR-ANP was higher in coronary sinus plasma than in femoral arterial plasma confirming that the heart was the source of the IR-ANP. The results support the hypothesis that IR-ANP is released from the heart by a direct effect of stretch of the atrial wall rather than by a neural or humoral mechanism involving a reflex from atrial receptors.     

Cardiovascular function in anesthetized miniature swine.

Miniature swine anesthetized with pentobarbital were studied with respect to their cardiovascular function under control conditions and in response to catecholamines, baroreceptor inhibition, bilateral vagotomy and vagal nerve stimulation. Measurements included aortic pressure, heart rate, intraventricular pressure and its maximum rate of rise during contraction, carotid blood flow and resistance, femoral blood flow and resistance, and renal blood flow and resistance. The cardiovascular actions of norepinephrine, epiniphrine and isoproterenol were similar to those in other mammals, and the adrenergic receptor mechanisms also were susceptible to blockade with phentolamine or propranolol. Inhibition of the carotid baroreceptors was accompanied by elevation of aortic pressure, reflex bradycardia and increased femoral and renal resistances. Bileteral vagotomy was followed by hypertension, tachycardia and increased renal resistance. Changes in femoral resistance to these procedures differed between the two strains of miniature swine studied. Stimulation of the peripheral end of either vagus nerve was accompanied by bradycardia without hypotension.     

Functional mechanism of expiratory pattern generator

Tidal expiratory activity and the time to its peak (TEa, i.e., time of active expiration) were measured from the integration curve of external oblique muscle activity in rabbits. The rabbits were spontaneously breathing under urethan-chloralose anesthesia in the prone position. CO2 rebreathing was performed, and the changes in the temporal profile of the integrated expiratory activity were studied. Hypercapnia increased the tidal expiratory activity before and after bilateral vagotomy. Before vagotomy, the rate of rise (tidal expiratory activity/TEa) increased significantly and TEa was shortened. On the other hand, after vagotomy, the rate of rise remained unchanged and TEa was prolonged. An expiratory off-switch model is postulated according to the quantitative relationship between the time and amplitude of the tidal expiratory activity. The expiratory activity pattern in vagotomized rabbits was similar to that in humans.     

Morphologic and histochemical indices of hepatic function following bilateral subdiaphragmatic vagotomy

A complex morpho-functional investigation of the rat liver was performed after bilateral subdiaphragmal vagotomy by means of light, electron microscopy methods and a quantitative histochemical method. Some ultrastructural disorders in hepatocytes and in stellate reticuloendotheliocytes were revealed, with their maximal manifestation 7 days after vagotomy. At later stages (45 and 90 days), compensatory-restorative processes develop resulting in considerable (but not complete) normalization of the organ's structure. Quantitative histochemical investigations have demonstrated that even at the highest degree of the resulted disorders the liver preserves its ability to synthesize and accumulate glycogen, but the intensity of the process is considerably lowered. Functional changes are reversible in their character and correlate to the degree of structural disorders.     

Ultrastructural alterations of the pancreatic D cell in the domestic fowl following vagotomy

Summary In an attempt to determine the neural control of pancreatic D cells, the pancreatic islets of the domestic fowl were examined electron microscopically from 1 to 28 days after abdominal vagotomy. Exocytotic release of many secretory granules from D cells occurred one day after vagotomy. Rough endoplasmic reticulum developed and formed an arrangement of concentric whorls in the cytoplasm of D cells after axotomy. The altered D cells were also characterized by the occurrence of many peculiar dense bodies in the apical cytoplasm at all time periods studied. These bodies varied in shape and size, containing several round vesicles. The D cells were extensively depleted of granules after the longer time periods following vagotomy. The present results provide new morphological evidence for the vagus-nerve control of D cells, which may regulate the activity of islet cells.     

Altered cardiovascular reflex responses during positive pressure breathing

Cardiovascular responses during hyperinflation produced by positive end-expiratory pressure (PEEP) are considered to be reflexly influenced by pulmonary mechanoreceptors. Numerous studies have indicated heart and vascular effects attributed to mechanical events and cardiopulmonary mechanoreflexes. Yet interactions of these modalities with the systemic baroreflexes are not clear. We examined aspects of these modulatory interactions by distinguishing changes in pulmonary, heart, and vascular responses during PEEP-hyperinflation before and after progressive elimination of chemo-, mechano-, and baroreflex influences in the closed-chest anesthetized rabbit. During respiratory alkalosis PEEP was imposed in increments of 2.5 cm H2O (range 0.0 to 7.5 cm H2O) before and during control of carotid intrasinus pressure and following aortic denervation and vagotomy. Heart rate responses during PEEP increased prior to aortic denervation, decreased following elimination of baroreflexes, and were abolished after vagotomy. The fall in mean arterial pressure (MAP) during PEEP was accentuated during elimination of the baroreflexes and ameliorated following vagotomy. Mean right atrial (MRAP), intrapleural (MIP), and right atrial transmural pressure increased during PEEP prior to vagotomy. Regression analyses of MAP versus MRAP and MAP versus MIP suggest that vagally receptors reflexly influence venous as well as systemic arterial vascular pressure. Conclusion indicate that when superimposed on mechanical events, cardiopulmonary mechanoreceptors and arterial baroreceptors effect conflicting facilitory reflex influences on heart and vascular responses during PEEP-hyperinflation.