The paraganglia within the carotid bifurcation regions of young and old spontaneously hypertensive rats (SHR) after exposure to chronic hypobaric hypoxia. I. The carotid bodies

Carotid body volumes and the histological appearance of these chemoreceptors were studied using light microscopic methods in 10 groups of spontaneously hypertensive rats (SHR). The aim of this study was to clarify the influence of chronic hypobaric hypoxia on the carotid bodies of SHR depending on the age of the rats, on the duration of exposure to hypoxia, and on different salt intake, respectively different blood pressure. We found that: 1. The carotid bodies of chronically hypoxic SHR are enlarged. 2. The degree of carotid body enlargement is dependent on the duration of exposure to hypoxia. 3. In old SHR the increase of carotid body volume was smaller than in young SHR. 4. Old chronically hypoxic SHR exhibited more distinct vascular changes in the carotid bodies than age-matched normoxic controls as well as younger chronically hypoxic and normoxic SHR. 5. The influence of different levels of systemic arterial blood pressure on the carotid body volumes was rather small compared with the effects of chronic hypobaric hypoxia.     

The aortic bodies of spontaneously hypertensive (SHR) and normotensive rats--a study concerning location and size

The aortic bodies, including the right and left subclavian bodies and the superior aorticopulmonary bodies, were examined in inbred normotensive control rats (NCR) of the Wistar strain and in spontaneously hypertensive rats (SHR) of the OKAMOTO-AOKI strain. Paraganglia were found in all rats of either group. They were located near to the left common carotid artery and less frequently between the branching right subclavian and right common carotid artery. Superior aorticopulmonary bodies were rarely seen. No significant differences were found regarding the volume of individual aortic bodies when comparing these paraganglia in NCR and SHR. However, aortic bodies are more numerous in SHR and therefore the total volume of aortic body tissue per rat is significantly larger in this strain. There was good correlation between the total volume of aortic bodies and the total volume of carotid bodies in both strains of rats studied. These findings indicate, that the paraganglionic system as a whole is enlarged in SHR. This enlargement probably is caused genetically and not a result of increased blood pressure.     

Paraganglia of the rat recurrent laryngeal nerve after long-term hypoxia: A morphometric and biochemical study

Summary Paraganglia of the recurrent laryngeal nerve of rats exposed to hypoxia (10±0.5% O₂) for 3 weeks became enlarged in volume by 2.6-fold. The volume densities of blood vessel lumen and endothelial cells were unchanged. The enlargement of the paraganglia was mainly attributed to hypertrophy of the dense-cored vesicle-containing cell. Concerning the profile diameter of the vesicle, a unimodal distribution of dense-cored vesicle cells was found in both control and hypoxic paraganglia. The vesicle diameter increased by about 19%, whereas the numerical density of dense-cored vesicles and the vesicle volume density were unaltered after hypoxia.Recurrent laryngeal nerves assayed by a sensitive high performance liquid chromatography technique contained an average of 1.9pmol dopamine and 1.3pmol norepinephrine. Exposure to 2 weeks of hypoxia increased the dopamine level to 4.9pmol, whereas the norepinephrine content was unchanged. It is suggested from this study that the catecholamines determined are housed in the paraganglia of the recurrent laryngeal nerve.     

The effect of aging on extra-adrenal catecholamine storing cells of the rat

Cell number and catecholamine histofluorescence were determined in three extra-adrenal chromaffin tissues: the abdominal paraganglia, the carotid body and SIF (small intensely fluorescent)-cells, of male Fischer-344 rats at different ages. Catecholamines were demonstrated using the formaldehyde-induced fluorescence method. The number of paraganglia cells in the retroperitoneal area increased 13.6 fold between 3 and 33 months of age, and the volume of abdominal paraganglia approached 65% of the volume of one adrenal medulla. The emission color of some paraganglia cells shifted from greenish-yellow to yellowish-brown with aging, but differences were not observed in cell number of fluorophore color in the carotid body, a chemoreceptor type of paraganglion. The number of SIF cells (an intraganglionic variant of extra-adrenal chromaffin tissue) in the hypogastric ganglion increased significantly between 3 and 33 months. The pronounced increase of the volume of the paraganglia in aged rats may contribute to elevated concentrations of circulating catecholamines in these animals.     

Hyperplasia of vagal and carotid body paraganglia in patients with chronic hypoxemia

Vagal and carotid body paraganglia were obtained from 43 randomly selected autopsies performed at the National Naval Medical Center. In each case, tissue from both sides was step sectioned and comparatively studied. The mean combined weight of carotid bodies in 37 control patients was 25.9 mg. There was good correlation between size and number of separate paraganglia comprising the vagal body (seven left, six right). Lobules were closely related to the ganglion nodosum and were actually within it in three instances. Tissue resembling parathyroid was encountered within 4 of the 86 resected vagus nerves. Lymphocytic infiltration occurred in carotid and vagal body paraganglia of 28% and 16% of patients, respectively. There was Schwann cell proliferatation in carotid body lobules of 2 patients; in another patient, talc emboli were present. The mean combined weight of carotid bodies in 6 patients with chronic hypoxemia was 47.6 mg, significantly greater than in the control group; in each case, lobules were enlarged. Chief cell hyperplasia occurred in vagal body paraganglia of 2 patients; in two other patients, lobules were large with equal proliferation of constituent cells. These morphologic findings indicate that in patients with chronic hypoxemia some vagal body paraganglia can be ascribed a chemoreceptor role similar to but probably less important than that of the carotid body.     

Morphology of the carotid sinus wall in normotensive and spontaneously hypertensive rats

The morphology of the carotid sinus region of the internal carotid artery was studied in spontaneously hypertensive rats (SHR) at 5, 8, 16, and 24 weeks of age. The carotid sinus region occupied the proximal millimeter of the internal carotid artery, and was easily recognizable by the presence of an extensive adventitial capillary plexus, which was absent on adjacent arteries (e.g., common and external carotid arteries). Methylene blue-stained whole-mount preparations showed the extent of baroreceptor nerves over the sinus. Baroreceptor fibers terminated in distinctive bulbous-like endings, which, at the ultrastructural level, were filled with mitochondria. No differences were noted in the sinus adventitial capillary network or baroreceptor distribution between SHR and age-matched Wistar-Kyoto (WKY) normotensive control animals. With the onset of a significant rise in SHR blood pressure, the carotid sinus wall increased in thickness and total vessel size. The wall/lumen ratios were significantly larger in the SHR than in age-matched WKY ratios in all age groups. SHR carotid sinus vessel enlargement was uniform throughout the vessel tunics, with no significant change in the proportion of the tunica media occupied by smooth muscle cells. The increase in the carotid sinus wall thickness associated with increasing hypertension could affect the ability of the sinus to distend and may play a secondary role in the maintenance of hypertension by compromising baroreceptor nerve ending sensitivity.     

Stimulus-specific signaling pathways in rabbit carotid body chemoreceptors

The carotid body is an arterial chemosensory organ which responds to multiple natural and pharmacological stimuli, including hypoxia and nicotine. Numerous studies have investigated the initial molecular events which activate chemosensory type I cells in the carotid body, but less attention has been focused on later steps in the transduction cascade, which mediate neurotransmitter release from type I cells and excitation of chemoreceptor afferent fibers in the carotid sinus nerve. In the present study, we examined the effects of a highly specific inhibitor of calcium/calmodulin-dependent kinase II, KN-62, and a calmodulin inhibitor, trifluoperazine, on carotid sinus nerve activity and catecholamine release evoked from rabbit carotid bodies superfused in vitro. KN-62 did not alter sinus nerve activity and catecholamine release evoked by hypoxia, but this agent significantly reduced nerve activity and neurotransmitter release evoked by 100 microM nicotine. Trifluoperazine (10 microM), likewise inhibited activity evoked by nicotine, as well as hypoxia. Basal levels of nerve activity and catecholamine release (established in superfusate equilibrated with 100% O2) were unaffected by all drug treatments. Separate biochemical experiments showed that Ca2+/calmodulin-dependent incorporation of 32P into carotid body particulate proteins is significantly reduced following incubation of intact carotid bodies in nicotine, but not following exposure to hypoxia. Our observations suggest that excitation of the carotid body by diverse stimuli may involve the activation of distinct, stimulus-specific transduction pathways. Furthermore, these data correlate with our previous findings which showed that hypoxia, on the one hand, and nicotine on the other, evoke the preferential release of either dopamine or norepinephrine, respectively, from carotid bodies incubated in vitro.     

The carotid bodies of renal hypertensive rats

The carotid bodies of renal hypertensive rats (one kidney wrap model) were studied by light-microscopic and morphometric methods. Rats with established hypertension showed massive intraglomic vascular alterations, such as exudation of plasma, subendothelial fibrinoid deposits and fibrinoid necroses of the intima and media. Additionally a granuloma-like perivascular proliferation of fibroblasts and histiocytes was seen. The total carotid body volume was enlarged but the volume of the specific glomic tissue was reduced in comparison with normotensive controls. In rats with borderline hypertension similar pathological changes were found but in a more reduced extension. Additionally in these rats some intraglomic vessels showed an accumulation of acid mucopolysaccharides and an hyperplasia of mediocytes. Rats with such vessel alterations also exhibited a small enlargement of specific glomic tissue. In general the pathological changes of the carotid bodies in renal hypertensive rats are different in comparison with those in the glomera carotici of rats with spontaneous hypertension (SHR, GH rats). This study suggests that an elevated blood pressure does not solely cause an increment of the specific chemoreceptive tissue mass of the carotid bodies.     

Intra and juxtavagal paraganglia: a topographical, histochemical, and ultrastructural study in the human

The topographical, ultrastructural, and histochemical features of 23 human vagal paraganglia were analyzed. Nineteen of the 23 paraganglia were found in previously unreported sites; 18 of the 19 were in the cervical part of the nerve, between the carotid bifurcation and the superior thoraco-cervical inlet, and one paraganglion was located in the retrothyroidal part of the left inferior laryngeal nerve. The results of ultrastructural studies (2 cases), the histochemical and formaldehyde-induced-fluorescence studies (3 cases), and specific acetylcholinesterase activity (one case) demonstrate that these structures fulfill many of the modern criteria for paraganglionic tissue. In addition to paraganglia, single, isolated neurons or true micro-ganglia were always found along the trunk and branches of the vagus nerve when multiple sections were examined.     

Stimulus-specific signaling pathways in rabbit carotid body chemoreceptors

The carotid body is an arterial chemosensory organ which responds to multiple natural and pharmacological stimuli, including hypoxia and nicotine. Numerous studies have investigated the initial molecular events which activate chemosensory type I cells in the carotid body, but less attention has been focused on later steps in the transduction cascade, which mediate neurotransmitter release from type I cells and excitation of chemoreceptor afferent fibers in the carotid sinus nerve. In the present study, we examined the effects of a highly specific inhibitor of calcium/calmodulin-dependent kinase II, KN-62, and a calmodulin inhibitor, trifluoperazine, on carotid sinus nerve activity and catecholamine release evoked from rabbit carotid bodies superfused in vitro. KN-62 did not alter sinus nerve activity and catecholamine release evoked by hypoxia, but this agent significantly reduced nerve activity and neurotransmitter release evoked by 100 μM nicotine. Trifluoperazine (10 μM), likewise inhibited activity evoked by nicotine, as well as hypoxia. Basal levels of nerve activity and catecholamine release (established in superfusate equilibrated with 100% O₂) were unaffected by all drug treatments. Separate biochemical experiments showed that Ca²⁺/calmodulin-dependent incorporation of ³²P into carotid body particulate proteins is significantly reduced following incubation of intact carotid bodies in nicotine, but not following exposure to hypoxia.Our observations suggest that excitation of the carotid body by diverse stimuli may involve the activation of distinct, stimulus-specific transduction pathways. Furthermore, these data correlate with our previous findings which showed that hypoxia, on the one hand, and nicotine on the other, evoke the preferential release of either dopamine or norepinephrine, respectively, from carotid bodies incubated in vitro.     

Location and size of carotid body-like organs (paraganglia) revealed in rats by the permeability of blood vessels to Evans blue dye

Summary We determined the number, distribution, size, and morphology of paraganglia near the glossopharyngeal, vagus, and sympathetic nerves of rats. The location of paraganglia was revealed by a method that takes advantage of the comparatively high permeability of their blood vessels to Evans blue dye. Rats were fixed by vascular perfusion of glutaraldehyde 2 min after receiving an intravenous injection of Evans blue dye. Paraganglia appeared as circumscribed, intensely blue structures that were readily distinguished from unstained nerves associated with them. Similarly, some groups of small intensely fluorescent (SIF) cells in autonomic and sensory ganglia were surrounded by Evans blue at a time that other portions of the ganglia contained little detectable dye. An average of 92.5 (range 41–134) paraganglia and 41 (range 17–68) blue spots in ganglia were found in the neck, thorax and abdomen of each of 10 rats. Carotid bodies had a mean length of 601 ± 123 m, width of 275 ± 65 m, and volume of 25.1 ± 11.2,m³ × 10⁶. Other paraganglia had an average length of 168 ± 108m, width of 77 ± 41 m, and volume of 0.87 ± 1.55 m³ × 10⁶. The total volume of paraganglion tissue averaged 128 m³ × 10⁶ (range 62–215 m³ × 10⁶), 59% of which was due to paraganglia other than the carotid bodies.By using fluorescence microscopy, we verified that small catecholamine-containing cells, visible because of their yellow-green fluorescence induced by formaldehyde gas, were located in regions along nerves and within ganglia that contained extravascular dye, visible because of its red fluorescence. Electron-microscopic studies confirmed that blue-stained organs (presumptive paraganglia) associated with the superior laryngeal nerve and other branches of the vagus nerve contained cells morphologically similar to glomus cells of the carotid body. Celiac ganglia contained, in addition, some cells similar to chromaffin cells of the adrenal medulla. Paraganglia (but not SIF cells in ganglia) were encapsulated by layers of perineurium, which may constitute a barrier to diffusion. Tortuous thin-walled blood vessels, some with a fenestrated endothelium, were present in all paraganglia examined and were near most groups of SIF cells in ganglia. Neural connections of the small catecholamine-containing cells varied. Most nerve terminals on cells in paraganglia resembled sensory nerve endings on glomus cells of the carotid body, although some were morphologically similar to preganglionic nerves on chromaffin cells of the adrenal medulla.     

The relative roles of the aortic and carotid sinus nerves in the rabbit in the control of respiration and circulation during arterial hypoxia and hypercapnia

1. The respiratory and circulatory effects of graded arterial hypoxia, alone or with superadded hypercapnia, were studied in four groups of unanaesthetized rabbits including normal animals and those with selective section of the aortic nerves, selective section of the carotid sinus nerves and section of both sets of nerves.

2. When measured 2-4 days after selective section of the carotid sinus nerves the resting respiratory minute volume and arterial P_O2 were lower and the P_CO2 higher than normal. These effects were not observed after selective section of the aortic nerves. Selective aortic nerve section, and selective carotid sinus nerve section each produced a similar increase in the resting arterial pressure and heart rate, but were without effect on the resting cardiac output.

3. During arterial hypoxia reflex respiratory and circulatory effects ascribable to arterial chemoreceptor stimulation (hyperventilation, bradycardia, vasoconstriction) were mediated for the most part through the carotid sinus nerve. In animals with only the aortic nerves intact the circulatory response was determined largely by the opposing effects of aortic baroreceptor reflexes and the local peripheral dilator action of hypoxia.

4. The circulatory effects of hyperventilation induced by hypercapnia during arterial hypoxia, in animals with both aortic and carotid sinus nerves cut were small.

5. The results suggest that relatively few chemoreceptor fibres originate from the aortic region in the rabbit, though the carotid sinus and aortic nerves both contain baroreceptor fibres.

     

Morphometric analysis of glomus cells within the recurrent laryngeal nerve of the rat

Summary An endoneurial paraganglion located in the recurrent laryngeal nerve of the rat was found in 17 of 20 nerves studied. The median size of the paraganglia was estimated to be 0.8 × 10⁶ m³. The number of type I like cells within a paraganglion ranged between 8 and 24. Altogether, 120 endoneurial dense-cored vesicle cells from 8 paraganglia were subjected to a morphometric analysis at the ultrastructure level. The mean vesicle profile diameter was estimated to be 101.3 nm and only one type of granulated cell could be distinguished. The volume density of the dense-cored vesicles was estimated to be about 6%, a value amounting to two to three times that in the carotid glomus. Moreover, the mean cell profile area of vesiculated cells of recurrent laryngeal nerve exceeds that of the cells of the carotid glomus.     

Acute hypoxia elevates nitric oxide generation in rat carotid body in vitro

In acute hypoxia, the release of nitric oxide (NO) produced in rat carotid body is unclear. The concentration of NO was measured electrochemically with a Pt/Nafion/Pd-IrOx/POAP-modified electrode placed on the surface of isolated carotid bodies superfused with bicarbonate-buffer saline at 35 degrees C. In hypoxia, the concentration of NO in the carotid body was increased by 17+/-2 nM. The amount of NO release during hypoxia was augmented by increasing the number of carotid bodies surrounding the electrode and also in the presence of L-arginine. In addition, the hypoxia-induced elevation of NO was abolished by pretreatment with a nitric oxide synthase (NOS) inhibitor, L-N(G)-nitroarginine methylester (L-NAME). The results suggest that endogenous NO production in the carotid body increases during hypoxia. Electrophysiological measurement of single fiber activity in the sinus nerve revealed that L-NAME treatment enhances the afferent discharge in response to hypoxia. This confirms that the hypoxia-induced elevation of NO suppresses the carotid chemoreceptor response to hypoxia. Taken together, it is concluded that acute hypoxia increases NO generation in the rat carotid body, and that the elevated levels of NO suppress carotid chemoreceptor activity during hypoxia. Hence, NO may play an active inhibitory role in the control of carotid chemoreceptor activity during hypoxia.     

Pronounced depression by propofol on carotid body response to CO2 and K+-induced carotid body activation

Propofol is a commonly used anesthetic agent, and it attenuates hypoxic ventilatory response in humans. Propofol reduce in vivo and in vitro carotid body responses to hypoxia as well as to nicotine in experimental animals. In the present study we examined the effects of propofol on carotid body responses to hypercapnia and K(+)-induced carotid body activation and compared these effects with hypoxia in an in vitro rabbit carotid body preparation. Hypoxia, hypercapnia and potassium increased the carotid sinus nerve activity and propofol attenuated the chemoreceptor responses to all three stimuli. However, the magnitude of propofol-induced attenuation was greater for hypercapnic and K(+)-induced carotid body activation compared to the hypoxic response. These observations suggest that propofol-induced attenuation of the hypoxic response is partly secondary to depression of chemoreceptor response to hypercapnia inhibiting the synergistic interactions between O(2) and CO(2) and may involve CO(2)/H(+) sensitive K(+) channels.     

Calcium handling by the cat carotid body--a pyroantimonate study

Subcellular regulation mechanisms of calcium concentrations related to oxygen sensing in the carotid body are unclear. In the present study, we investigated the ultrastructural distribution patterns of calcium in carotid body cells and its changes evoked by hypoxia. Carotid bodies were dissected from anesthetized cats exposed in vivo to normoxic or acute hypoxic conditions. We used the oxalate-pyroantimonate technique that yields an electron-opaque calcium precipitate. X-ray microanalysis and appropriate controls confirmed the presence of calcium in the precipitate. Calcium precipitates were found in all types of cells in carotid body parenchyma: chemoreceptor cells, sustentacular cells, and nerve endings. In normoxic chemoreceptor cells, the precipitate was localized in dense core vesicles, mitochondria, and nuclei, but rarely in the cytoplasm. The most apparent effect of hypoxia was disappearance of the precipitate from dense core vesicles and was associated with its appearance in the cytoplasm. The amount of precipitate throughout the carotid body parenchyma was decreased overall due to hypoxia. These results indicate the involvement of subcellular calcium trafficking in hypoxia-sensing in the carotid body. The redistribution pattern of granular calcium deposits from organelles to the cytoplasm of chemoreceptor cells agrees with biochemical data of calcium release from intracellular stores during hypoxia.     

A quantitative morphological study of the carotid bodies of rats living at a simulated altitude of 4300 metres.

A quantitative histological study was carried out on the carotid bodies of 10 normal rats and 10 rats living in a hypobaric chamber at a pressure of 460 mm Hg from 25 to 96 days. In the chronically hypoxic rats there was a four-fold increase in the mean combined volume of the carotid bodies. Morphometric analysis disclosed a three-fold increase in the mean volume of specialised glomic cells and a ten-fold increase in the mean volume of capillaries, although the proportion of glomic cells was actually significantly decreased. In all our hypoxic rats there was evidence of both right and left ventricular hypertrophy. However, there was no linear relation between total carotid body volume or volume of glomic cells on one hand and the right and left ventricular weight, on the other hand. Although there was no linear relation between combined total carotid body volume and duration of hypoxia, the linear relation between glomic cell volume and duration of hypoxia was significant at the 5 per cent. level. The increase in vascularity of the hypoxic carotid body may be a mechanism to increase blood flow and thus oxygen transport to a hypoxic organ with increased metabolic activity. Small quantities of an amorphous hyaline material of unknown nature were found in relation to capillaries and type I cells in all the hypoxic rats.     

Carotid sinus nerve responses and ventilatory acclimatization to hypoxia in adult rats following 2 weeks of postnatal hyperoxia

Adult rats have decreased carotid body volume and reduced carotid sinus nerve, phrenic nerve, and ventilatory responses to acute hypoxic stimulation after exposure to postnatal hyperoxia (60% O2, PNH) during the first 4 weeks of life. Moreover, sustained hypoxic exposure (12%, 7 days) partially reverses functional impairment of the acute hypoxic phrenic nerve response in these rats. Similarly, 2 weeks of PNH results in the same phenomena as above except that ventilatory responses to acute hypoxia have not been measured in awake rats. Thus, we hypothesized that 2-week PNH-treated rats would also exhibit blunted chemoafferent responses to acute hypoxia, but would exhibit ventilatory acclimatization to sustained hypoxia. Rats were born into, and exposed to PNH for 2 weeks, followed by chronic room-air exposure. At 3-4 months of age, two studies were performed to assess: (1) carotid sinus nerve responses to asphyxia and sodium cyanide in anesthetized rats and (2) ventilatory and blood gas responses in awake rats before (d0), during (d1 and d7), and 1 day following (d8) sustained hypoxia. Carotid sinus nerve responses to i.v. NaCN and asphyxia (10 s) were significantly reduced in PNH-treated versus control rats; however, neither the acute hypoxic ventilatory response nor the time course or magnitude of ventilatory acclimatization differed between PNH and control rats despite similar levels of PaO2 . Although carotid body volume was reduced in PNH rats, carotid body volumes increased during sustained hypoxia in both PNH and control rats. We conclude that normal acute and chronic ventilatory responses are related to retained (though impaired) carotid body chemoafferent function combined with central neural mechanisms which may include brainstem hypoxia-sensitive neurons and/or brainstem integrative plasticity relating both central and peripheral inputs.     

Evidence for central reorganization of ventilatory chemoreflex pathways in the cat during regeneration of visceral afferents in the carotid sinus nerve

There are two sets of peripheral arterial chemoreceptors in the cat, the carotid bodies innervated by the carotid sinus nerve and the aortic bodies with afferents in the aortic depressor nerves. Reflex stimulation of ventilation in response to hypoxia is abolished acutely after interrupting the sensory pathway from the carotid body chemoreceptors in the cat even though the reflex pathway from the aortic body chemoreceptors is intact. However, in chronically maintained preparations, there is a restoration of the hypoxic response which is mediated by the aortic chemoreflex pathway. It was proposed that restoration was due to a ‘central reorganization’ of chemoreflex pathways which followed interruption of the sensory pathway from the carotid bodies and that the reorganization enhanced the efficacy of the aortic ventilation chemoreflex. This proposal was tested in the present experiments by measuring reflex ventilatory and cardiovascular responses to electrical stimulation of the sensory nerves containing aortic and carotid chemoreceptor afferents following bilateral interruption of carotid sinus nerves and carotid body resection. Responses measured acutely (1–6 h) after interruption were compared with those measured 60–80 and 110–140 days later. At 60–80 days, a chemoreflex response (increase in tidal volume of ventilation) to stimulation of the interrupted carotid sinus sensory pathway was markedly attenuated while the response to stimulation of the uninterrupted pathway in aortic depressor nerves was enhanced. At 110–140 days, the tidal volume response to carotid sinus nerve stimulation was greatly enhanced while the aortic depressor nerve response declined from the elevated level. There were significant but less pronounced changes in the response of other ventilatory and cardiovascular variables to aortic depressor nerve and carotid sinus nerve stimulation.The results support the idea that there is a ‘central reorganization’ of chemoreflex pathways which is reflected functionally by changes in the efficacy of reflexes evoked from aortic depressor nerve and carotid sinus nerve. The changes are analagous to those occurring in somatic reflexes during regeneration of sensory nerves. It is suggested that the changes in efficacy of carotid sinus nerve reflexes are due to a degenerative loss of synapses of the central projections of interrupted carotid sinus nerve sensory axons (degenerative atrophy) and subsequent regenerative like changes (regenerative proliferation) in the central projections. The changes in the efficacy of aortic depressor nerve reflexes may be attributed to formation of new synapses by converging central projections of this uninterrupted pathway (reactive synaptogenesis) and subsequent regression of the newly formed synapses.     

Characteristics of inspiratory inhibition by occlusion of both external carotid and basilar arteries in cats.

Effects of the occlusion of both the external carotid and basilar arteries on the inspiratory activity were studied in anesthetized, vagotomized, paralyzed, and artificially ventilated cats. Integrated phrenic nerve activity was used as an index of the inspiratory activity. Blood pressure in the lingual artery, located downstream from the occluded external carotid arteries, was measured as the arterial pressure of the upper brain stem during occlusion. The basilar artery was occluded at the boundary between the medulla and pons. Occlusions of the external carotid arteries and basilar artery suppressed the phrenic nerve activity to finally disappear within 1 min (phrenic nerve apnea, 45 out of 50 occlusions in 6 cats). The blood pressure in the upper brain stem was 16.6 +/- 5.7 mmHg (mean +/- S.D.) during occlusions. These effects of occlusion on the phrenic nerve activity were also observed during hypercapnia and hypoxia, although they were not so remarkable as those during normocapnia and normoxia. The results indicate that the upper part of the brain stem operates a profound facilitatory mechanism on the medullary inspiratory activity.