Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery.

BACKGROUND: Control of peripheral resistance arteries by autonomic nerves is essential for the regulation of blood flow. The signals responsible for the maintenance of vascular neuroeffector mechanisms in the adult, however, remain largely unknown. METHODS AND RESULTS: Here, we report that VEGF( partial differential/ partial differential) mice with low vascular endothelial growth factor (VEGF) levels suffer defects in the regulation of resistance arteries. These defects are due to dysfunction and structural remodeling of the neuroeffector junction, the equivalent of a synapse between autonomic nerve endings and vascular smooth muscle cells, and to an impaired contractile smooth muscle cell phenotype. Notably, short-term delivery of a VEGF inhibitor to healthy mice also resulted in functional and structural defects of neuroeffector junctions. CONCLUSIONS: These findings uncover a novel role for VEGF in the maintenance of arterial neuroeffector function and may help us better understand how VEGF inhibitors cause vascular regulation defects in cancer patients.

Effects of cold pressor-induced sympathetic stimulation on the mechanical properties of common carotid and femoral arteries in healthy males.

Our aim was to evaluate the effects of sympathetic excitation and elevation of blood pressure on mechanical properties of common carotid and femoral arteries by wave intensity analysis (WIA). The diameters and arterial stiffness parameters of right common carotid artery (RCCA) and right common femoral artery (RCFA) in healthy young men were measured by WIA at baseline and during cold pressor test (CPT). In addition, the blood pressure and heart rate were recorded simultaneously. The heart rates and blood pressures increased during CPT compared with baseline, while the pulse pressures remained unchanged. The diameters of RCCA increased slightly, while those of RCFA did not change. The Peterson's pressure modulus (Ep), augment index (AI), and pulse wave velocity from ß (PWVß) increased obviously, while arterial compliance (AC) decreased with no change in stiffness index (ß) of both arteries during CPT when compared with baseline. There was an obvious increase in pulse wave velocity from wave intensity (PWV_WI) of RCCA, while the PWV_WI of RCFA showed no significant change during CPT. The sympathetic nervous system exerts a more marked tonic restraint on RCFA than on RCCA. The Ep, AC, AI, PWVß of RCCA, and RCFA are much affected by variations in blood pressure and sympathetic status, while the ß of both arteries are less vulnerable to these factors and are more reliable in reflecting the actual arterial stiffness; The PWV_WI appears to be suitable only for evaluating the stiffness of RCCA instead of RCFA.

Baroreceptor and chemoreceptor contributions to the hypertensive response to bilateral carotid occlusion in conscious mice.

This study aimed to characterize the role played by baroreceptors and chemoreceptors in the hypertensive response to bilateral carotid occlusion (BCO) in conscious C57BL mice. On the day before the experiments the animals were implanted with pneumatic cuffs around their common carotid arteries and a femoral catheter for measurement of arterial pressure. Under the same surgical approach, groups of mice were submitted to aortic or carotid sinus denervation or sham surgery. BCO was performed for 30 or 60 s, promoting prompt and sustained increase in mean arterial pressure and fall in heart rate. Compared with intact mice, the hypertensive response to 30 s of BCO was enhanced in aortic-denervated mice (52 ± 4 vs. 41 ± 4 mmHg; P < 0.05) but attenuated in carotid sinus-denervated mice (15 ± 3 vs. 41 ± 4 mmHg; P < 0.05). Suppression of peripheral chemoreceptor activity by hyperoxia [arterial partial pressure of oxygen (Pa(O(2))) > 500 mmHg] attenuated the hypertensive response to BCO in intact mice (30 ± 6 vs. 51 ± 5 mmHg in normoxia; P < 0.05) and abolished the bradycardia. It did not affect the hypertensive response in carotid sinus-denervated mice (20 ± 4 vs. 18 ± 3 mmHg in normoxia; P < 0.05). The attenuation of the hypertensive response to BCO by carotid sinus denervation or hyperoxia indicates that the hypertensive response in conscious mice is mediated by both baro- and chemoreceptors. In addition, aortic denervation potentiates the hypertensive response elicited by BCO in conscious mice.

Role of Blood Pressure in Mediating Carotid Artery Dilation in Response to Sympathetic Stimulation in Healthy, Middle-Aged Individuals.

OBJECTIVES: Carotid artery diameter responses to sympathetic stimulation, i.e., carotid artery reactivity (CAR), represent a novel test of vascular health and relates to cardiovascular disease (CVD)/risk. This study aims to understand the relationship between the increase in blood pressure and carotid artery diameter response during the CAR-test in healthy, middle-aged men. METHODS: Sample consisted of 40 normotensive men (aged 31-59 years) with no history of CVD of currently taking medication. Noninvasive ultrasound was used to measure carotid artery diameter during the cold pressor test (CPT), with CAR% being calculated as the relative change from baseline (%). Mean arterial pressure (MAP) was measured with beat-to-beat blood pressure recording. RESULTS: CAR% was 4.4 ± 5.4%, peaking at 92 ± 43 seconds. MAP increased from 88 ± 9 mmHg to 110 ± 15 mmHg, peaked at 112 ± 38 seconds, which was significantly later than the diameter peak (P = 0.04). The correlation between resting MAP and CAR% was weak (r = 0.209 P = 0.197). Tertiles based on resting MAP or MAP-increase revealed no significant differences between groups in subject characteristics including age, body mass index, or CAR% (all P > 0.05). Subgroup analysis of individuals with carotid constriction (n = 6) vs. dilation (n = 34), revealed no significant difference in resting MAP or increase in MAP (P = 0.209 and 0.272, respectively). CONCLUSION: Our data suggest that the characteristic increase in MAP during the CPT does not mediate carotid artery vasomotion.

Study of Effect of Sympathetic Nerve on Children's Brain Diseases Based on Analysis of Magnetic Resonance Imaging Kurtosis.

BACKGROUND: We evaluated the improvement in the gray and white matter functional areas in children with cerebral palsy (CP) after common carotid artery sympathetic neural network ablation. We also analyzed the relationship between the values of the diffusion kurtosis imaging (DKI) parameters and clinical signs in children with CP. METHODS: We collected data from 22 children with unilateral spastic CP who had undergone common carotid sympathetic neural network ablation in our hospital from January 1, 2014 to December 1, 2018, using magnetic resonance kurtosis imaging technology parameters. RESULTS: The study found that the changes from preoperatively to postoperatively in the kurtosis fractional anisotropy (KFA) values for the frontal lobe, parietal lobe, temporal lobe, internal sac forelimb, and corpus callosum were statistically significant. However, the changes in the internal sac forelimb, corpus callosum, and KFA values were not statistically significant. The changes from preoperatively to postoperatively in the mean kurtosis (MK) values for the frontal lobe, parietal lobe, temporal lobe, hindlimb of the internal capsule, corpus callosum, and caudate nucleus were statistically significant. However, the MK values for the forelimb, corpus callosum, and thalamus were not statistically significant. The 66-item gross motor function measure scores correlated negatively with the KFA value and positively with the MK value. CONCLUSION: Therefore, it can be concluded that DKI technology can more accurately reflect the gray and white matter damage in children with CP, and the DKI parameters can be used as a monitoring and evaluation index for children with CP.

Effect of bilateral carotid occlusion on cerebral hemodynamics and perivascular innervation: An experimental rat model.

We aimed to investigate the effect of chronic cerebral hypoperfusion on cerebral hemodynamics and perivascular nerve density in a rat model. Bilateral common carotid artery (CCA) ligation (n = 24) or sham-operation (n = 24) was performed with a 1-week interval. A subgroup (ligated n = 6; sham-operated n = 3) underwent magnetic resonance imaging (MRI) before the procedures and 2 and 4 weeks after the second procedure. After termination, carotids were harvested for assessment of complete ligation and nerve density in cerebral arteries that were stained for the general neural marker PGP 9.5 and sympathetic marker TH by computerized image analysis. Five rats were excluded because of incomplete ligation. MRI-based tortuosity of the posterior communicating artery (Pcom), first part of the posterior cerebral artery (P1) and basilar artery was observed in the ligated group, as well as an increased volume (p = 0.05) and relative signal intensity in the basilar artery (p = 0.04; sham-group unchanged). Immunohistochemical analysis revealed that compared to sham-operated rats, ligated rats had increased diameters of all intracircular segments and the extracircular part of the internal carotid artery (p < 0.05). Ligated rats showed a higher general nerve density compared to controls in P1 (10%, IQR:8.7-10.5 vs. 6.6%, IQR:5.5-7.4, p = 0.003) and Pcom segments (6.4%, IQR:5.8-6.5 vs. 3.2%, IQR:2.4-4.3, p = 0.003) and higher sympathetic nerve density in Pcom segments (3.7%, IQR:2.8-4.8 vs. 1.7%, IQR:1.3-2.2, p = 0.02). Bilateral CCA occlusion resulted in redistribution of blood flow to posteriorly located cerebral arteries with remarkable changes in morphology and perivascular nerve density, suggesting a functional role for perivascular nerves in cerebral autoregulation.

Effects of sinoaortic denervation on hemodynamic parameters during natural sleep in rats.

STUDY OBJECTIVES: To analyze the role of arterial baroreflex on hemodynamic changes during synchronized and desynchronized sleep phases of natural sleep in rats. DESIGN: Experimental study. SETTING: Laboratory. PARTICIPANTS: Seventeen male Wistar rats. INTERVENTIONS: No intervention (control, n = 8) or sinoaortic denervation (SAD, n = 9). MEASUREMENTS AND RESULTS: Sleep phases were monitored by electrocorticogram, and blood pressure was measured directly by a catheter in the carotid artery. Cardiac output, as well as total and regional vascular resistances, were determined by measuring the subdiaphragmatic aorta and iliac artery flows with Doppler flow probes, respectively. In contrast to the control group, the SAD group had a strong reduction in blood pressure (-19.9% +/- 2.6% vs -0.7% +/- 2.1%) during desynchronized sleep, and cardiac output showed an exacerbated reduction (-10.4% +/- 3.5% vs 1.1% +/- 1.7%). In SAD rats, total vascular resistance decreased during desynchronized sleep (-10.1% +/- 3.5% vs -1.0% +/- 1.7%), and the increase in regional vascular resistance observed in the control group was abolished (27.5% +/- 8.3% vs -0.8% +/- 9.4%). CONCLUSIONS: SAD caused profound changes in blood pressure, cardiac output, and total vascular resistance, with a significant increase in muscle vascular resistance during synchronized sleep. Our results suggest that baroreflex plays an important role in maintaining the normal balance of cardiac output and total vascular resistance during sleep.

Serotonin type 1D receptors (5HTR) are differentially distributed in nerve fibres innervating craniofacial tissues.

We tested the hypothesis that the 5HT(1D)R, the primary antinociceptive target of triptans, is differentially distributed in tissues responsible for migraine pain. The density of 5HT(1D)R was quantified in tissues obtained from adult female rats with Western blot analysis. Receptor location was assessed with immunohistochemistry. The density of 5HT(1D)R was significantly greater in tissues known to produce migraine-like pain (i.e. circle of Willis and dura) than in structures in which triptans have no antinociceptive efficacy (i.e. temporalis muscle). 5HT(1D)R-like immunoreactivity was restricted to neuronal fibres, where it colocalized with calcitonin gene-related peptide and tyrosine hydroxylase immunoreactive fibres. These results are consistent with our hypothesis that the limited therapeutic profile of triptans could reflect its differential peripheral distribution and that the antinociceptive efficacy reflects inhibition of neuropeptide release from sensory afferents. An additional site of action at sympathetic efferents is also suggested.

Nitric oxide and glutamate in the dorsal facial area regulate common carotid blood flow in the cat.

Nitric oxide (NO) or glutamate stimulation of dorsal facial area (DFA) increases blood flow in the common carotid artery (CCA), which supplies intra-and extra-cranial tissues. Nitrergic fibers and neurons as well as preganglionic cholinergic neurons are present in the DFA. We hypothesized the presence of nitrergic-glutamatergic fibers and preganglionic nitrergic-cholinergic neurons in the DFA that are involved in the regulation of CCA blood flow. In microdialysis studies, perfusion of the DFA with S-nitroso-N-acetylpenicillamine (SNAP, an NO donor) increased the glutamate concentration in the dialysate. This effect was abolished by co-perfusion of methylene blue (a guanylyl cyclase inhibitor). Intra-DFA injection of l-arginine (an NO precursor) or glutamate increased CCA blood flow. The l-arginine-induced flow increase was reduced by prior administration of NG-nitro-arginine methyl ester (l-NAME, a non-specific NO synthase inhibitor), 7-nitroindazole (7-NI, a relatively selective neuronal NO synthase inhibitor), d-2-amino-5-phosphonopentanoate (d-AP5, a competitive NMDA receptor antagonist), or glutamate diethylester (GDEE, a competitive AMPA receptor antagonist). The glutamate-induced blood flow increase was reduced by prior administration of l-NAME, 7-NI, or methylene blue. The induced increase in CCA blood flow, however, was not affected by endothelial NO synthase inhibitor. The findings indicate that NO-signal transduction within the DFA might cause glutamate release from presynaptic nitrergic-glutamatergic fibres and that the released glutamate activates NMDA/AMPA receptors on preganglionic nitrergic-cholinergic neurons in the nucleus to activate neuronal NO synthase and guanylyl cyclase in the neurons, leading to an increase in CCA blood flow. These findings may be important for developing therapeutic strategies for the diseases associated with CCA blood flow.

In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium.

The goal of this method is to introduce a transgene into the endothelium of isolated segments of both rabbit common carotid arteries. The method achieves focal endothelial-selective transgenesis, thereby allowing an investigator to determine the biological roles of endothelial-expressed transgenes and to quantify the in vivo transcriptional activity of DNA sequences in large artery endothelial cells. The method uses surgical isolation of rabbit common carotid arteries and an arteriotomy to deliver a transgene-expressing viral vector into the arterial lumen. A short incubation period of the vector in the lumen, with subsequent aspiration of the lumen contents, is sufficient to achieve efficient and durable expression of the transgene in the endothelium, with no detectable transduction or expression outside of the isolated arterial segment. The method allows assessment of the biological activities of transgene products both in normal arteries and in models of human vascular disease, while avoiding systemic effects that could be caused either by targeting gene delivery to other sites (e.g. the liver) or by the alternative approach of delivering genetic constructs to the endothelium by germ line transgenesis. Application of the method is limited by the need for a skilled surgeon and anesthetist, a well-equipped operating room, the costs of purchasing and housing rabbits, and the need for expertise in gene-transfer vector construction and use. Results obtained with this method include: transgene-related alterations in arterial structure, cellularity, extracellular matrix, or vasomotor function; increases or reductions in arterial inflammation; alterations in vascular cell apoptosis; and progression, retardation, or regression of diseases such as intimal hyperplasia or atherosclerosis. The method also allows measurement of the ability of native and synthetic DNA regulatory sequences to alter transgene expression in endothelial cells, providing results that include: levels of transgene mRNA, levels of transgene protein, and levels of transgene enzymatic activity.

Extra- and intracranial blood flow regulation during the cold pressor test: influence of age.

We determined how the extra- and intracranial circulations respond to generalized sympathetic activation evoked by a cold pressor test (CPT) and whether this is affected by healthy aging. Ten young [23 ± 2 yr (means ± SD)] and nine older (66 ± 3 yr) individuals performed a 3-min CPT by immersing the left foot into 0.8 ± 0.3°C water. Common carotid artery (CCA) and internal carotid artery (ICA) diameter, velocity, and flow were simultaneously measured (duplex ultrasound) along with middle cerebral artery and posterior cerebral artery mean blood velocity (MCAvmean and PCAvmean) and cardiorespiratory variables. The increases in heart rate (~6 beats/min) and mean arterial blood pressure (~14 mmHg) were similar in young and older groups during the CPT (P < 0.01 vs. baseline). In the young group, the CPT elicited an ~5% increase in CCA diameter (P < 0.01 vs. baseline) and a tendency for an increase in CCA flow (~12%, P = 0.08); in contrast, both diameter and flow remained unchanged in the older group. Although ICA diameter was not changed during the CPT in either group, ICA flow increased (~8%, P = 0.02) during the first minute of the CPT in both groups. Whereas the CPT elicited an increase in MCAvmean and PCAvmean in the young group (by ~20 and ~10%, respectively, P < 0.01 vs. baseline), these intracranial velocities were unchanged in the older group. Collectively, during the CPT, these findings suggest a differential mechanism(s) of regulation between the ICA compared with the CCA in young individuals and a blunting of the CCA and intracranial responses in older individuals.NEW & NOTEWORTHY Sympathetic activation evoked by a cold pressor test elicits heterogeneous extra- and intracranial blood vessel responses in young individuals that may serve an important protective role. The extra- and intracranial responses to the cold pressor test are blunted in older individuals.

[The role of endothelial nitric oxide in neurogenic contractions of the carotid artery in rabbits during cooling]. / Uloha endotelového oxidu dusnatého v neurogénnych kontrackciách a. carotis králika pocas ochladenia.

The role of endothelial nitric oxide in contractions induced by endogenous noradrenaline released by transmural nerve stimulation (TNS) and by exogenous noradrenaline (NA) was studied in isolated rings of rabbit carotid artery during cooling. At 37 degrees C, TNS produced frequency-dependent contractions of artery. Endothelium removal or inhibition of nitric oxide synthase by NG-nitro-L-arginine methyl ester (L-NAME) significantly enhanced TNS-induced contractions. The magnitude of maximal contraction to exogenous NA was increased in L-NAME-treated intact rings. Cooling the incubation bath from 37 degrees C to 26 degrees C increased the magnitude of neurogenic contractions in intact rings. L-NAME increased further the magnitude of neurogenic contractions at 26 degrees C in intact, but not in denuded arterial rings. Similarly, L-NAME increased contractions induced by exogenous NA during cooling. The results suggest that the response of the carotid artery to noradrenergic stimulation is modulated by nitric oxide originating from endothelial cells at normal as well as reduced temperature. (Tab. 1, Fig. 6, Ref. 19.)

Branches of the vagus nerve destined for the heart and the adjoining great vessels in the house shrew, Suncus murinus, with reference to the terminology of the vagal cardiac branches.

In order to help to organize the understanding of the bewildering complexities of the innervation of the mammalian heart by the vagus nerve and to clear up of confusions as regards the vagus cardiac branches, we scrutinized these branches in the adult house shrew, Suncus murinus, under a stereomicroscope. A number of branches were given off from the vagus nerve not only to the heart, but also to the adjoining great vessels, both outflowing and inflowing. When compared from the developmental viewpoint, the basic conformations of these branches on two sides were found not to differ from each other, but rather presented a symmetrical configuration, the feature which has been ascertained also in mammalian embryos. Relying on developmental criteria, we classified them into the arterial porta-related and the venous porta-related groups, formulating a new terminology by naming them on the basis of their destination. This version of terminology allowed us to define the vagus cardiac branches of the house shrew more accurately than the current terminology (e.g., Nomina Anatomica), and seems to provide us a clue for clearing up confusions concerning the terminology of the vagus cardiac branches in mammals.

Role of the trigeminal system on posterior communicating artery remodelization after bilateral common carotid artery ligation.

OBJECTIVE: To examine whether or not there is a possible relationship between the neuron density of trigeminal ganglion (TGG) and the severity of posterior communicating artery (PComA) vasodilation values after permanent bilateral common carotid artery ligation (BCCAL). STUDY DESIGN: This study included 25 rabbits. Both the common carotid arteries of 20 rabbits were explored and denervated. Five animals served as controls. Permanent BCCAL was applied in 15 of the 20 rabbits, and the other 5 were used as the SHAM group without ligation. All animals were followed for 2 months and then sacrificed. Their brains and cranial nerves were extracted and fixed in 10% formalin solution. The relationship between PComA vasodilation values and TGG neuron densities were compared. RESULTS: Elongation, convolution and enlargement were detected in all the basilar arteries of all ligated animals and 2 from the SHAM group. On histopathogical examination vascular wall thinning, luminal enlargement, flattened inner elastic membrane, flattened vessel muscle cells, endothelial desquamation and intimal erosions were detected. An inverse relationship was discovered between the neuron density of TGG and the severity of PComA vasodilation index. CONCLUSION: BCCAL may lead to important beneficial and hazardous histomorphological changes at the posterior communicating artery. The high neuron density of TGG may provide a beneficial effect by facilitating PComA enlargement via its vasodilatory properties for the increase of decreased cerebral circulation, although this situation may be hazardous for certain subjects with congenital or acquired cerebrovascular pathologies.

Nicotine stimulation of the medulla increases blood flow of the common carotid artery in cats.

Microinjection of nicotine or glutamate into the dorsal facial area (DFA) of the medulla increases blood flow of common carotid artery (CCA). Whether there is a causal relationship between these two events is not known. Various agonists and antagonists for the nicotinic and glutamatergic receptors were microinjected through a four-barrel tubing into the DFA of anesthetized cats. Microinjections of nicotine [a non-selective nicotinic acetylcholine receptor (nAChR) agonist], choline (a selective alpha7-nAChR agonist), glutamate or KCl induced a modest increase in CCA blood flow. The nicotine- and choline-induced increases were reduced by alpha-bungarotoxin (an alpha7-nAChR antagonist) as well as MK-801 (a non-competitive NMDA receptor antagonist) or glutamate diethylester (a competitive AMPA/kainate receptor antagonist). The glutamate or KCl-induced increases were blocked by MK-801 and glutamate diethylester, but not by alpha-bungarotoxin. In conclusion, activation of nAChRs primarily via alpha7-nAChR caused a release of glutamate, which in turn activated NMDA and AMPA receptors, while cholinergic substance was not released into the DFA to activate the nicotinic receptor.

Glutamate release upon purinergic action in the dorsal facial area of the medulla increases blood flow in the common carotid artery in cats.

Interactions of glutamatergic and purinergic actions in the medulla regulate important cardiovascular functions. The glutamatergic action in dorsal facial area (DFA) of the medulla increases blood flow of common carotid artery (CCA) in cats. We hypothesized that interactions of glutamatergic and purinergic actions in the DFA may regulate the CCA blood flow. Purinergic and glutamatergic agonists and antagonists were microinjected into the DFA through a four-barrel tubing in anesthetized cats. Drug effects were evaluated by changes in the CCA blood flow. Microinjection with 20 nmol ATP or alpha,beta-methyleneATP (alpha,beta-MeATP, a P2 purinergic receptor agonist) induced an increase of the CCA blood flow. This increase was dose-dependently reduced by prior administration with 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX, a specific P1 purinergic receptor antagonist), or pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, a selective P2 purinergic receptor antagonist) as well as with MK-801 (a non-competitive NMDA receptor antagonist) or glutamate diethyl ester (GDEE, a competitive AMPA/kainate receptor antagonist). It was almost completely blocked by administrations with combined maximal doses of P1 and P2 receptor antagonists as well as NMDA and AMPA receptor antagonists. Nevertheless, P1 receptor agonist induced only mild and poorly reproducible increase in the CCA blood flow. In conclusion, prominent P2 and minor P1 purinergic receptors appear to be present in the DFA; the purinergic activation can mediate a release of glutamate that stimulates NMDA and AMPA to induce the increase of the CCA blood flows. These findings may provide important information for developing therapeutic strategy for diseases involving the CCA blood flow, such as hypertensive disease and cerebral ischemia.

Ultrastructural changes in nervous elements associated with the granular cells of the common carotid artery of the domestic fowl after distal vagal ganglionectomy.

Intramural granular cells of the left and right common carotid artery of the domestic fowl were examined with the electron microscope after left distal vagal ganglionectomy. The vast majority of the nerve fibers and endings associated with the granular cells of the left common carotid artery degenerated rapidly after ipsilateral ganglionectomy, indicating that they are derived from the left vagus. On the other hand, left distal vagal ganglionectomy resulted in transformation of the intramural granular cells of the right common carotid artery and the few nervous elements associated with them, into a typical chemoreceptor tissue. This tissue was made up of small granule (60-120 nm) containing cells associated with many nerve fibers, nerve endings and fenestrated capillaries. The nerve endings were of two types; presumptive afferent endings and adrenergic efferent endings. Both types of endings made synaptic junctions with the granular cells.

Poor ventilatory response to mild hypoxia may inhibit acclimatization at moderate altitude in elderly patients after carotid surgery.

Peripheral chemoreceptors (carotid bodies) are the main sensing organs for hypoxaemia. During carotid surgery, the carotic body in the bifurcation of the common carotid artery is often involved and damaged or destroyed. Animals lose their ability to adapt to high altitude after experimental denervation of the carotid bodies. The objective of our study was to evaluate the ability of human patients to adapt to moderate altitude after single side carotid surgery. Blood gas analysis at rest at 171 m and after car and cable car transport to 1600 m before and after carotid surgery was performed. Mean(s.d.) paO2 decreased insignificantly from 74.8(3.56) at 171 m altitude to 71.6(2.07) at 1600 m (P = n.s.), means(s.d.) paCO2 decreased significantly from 36.2(2.86) to 31.4(2.7) mmHg (P < 0.05) before carotid surgery. Months after surgery, a significant drop in paO2 occurred after identical passive exposure to moderate altitude: mean(s.d.) paCO2 at 171 m 74.4(3.65) mmHg, at 1600 m 65.8(3.70) mmHg (P < 0.01), paCO2 did not change significantly. Mean(s.d.) paCO2 at 171 m: 36.0(2.35), at 1600 m 36.2(2.86) mmHg (P = n.s.). Although the sample investigated was small, after single side carotid surgery patients seem to lose their ability for satisfactory ventilatory response to acute exposure to moderate altitude. This is of possible alpine medical importance.

Changes in intra- and extracranial tissue blood flow upon stimulation of a reticular area dorsal to the facial nucleus in cats.

1. A small area in the dorsal part of the lateral tegmental field specifically responsible for the increase of blood flow in the common carotid artery (CCA) without accompanying change in the resting blood pressure was first identified in our laboratory. Since the area is located just dorsal to the facial nucleus, we named it the dorsal facial area (DFA; Kuo et al. 1987). 2. The purpose of this study was to clarify whether an increase of blood flow in intra- and/or extracranial tissues was responsible for the increase in CCA blood flow upon DFA stimulation, and to determine the role of cholinergic transmission in this response. 3. In 20 cats under chloralose and urethane anaesthesia, microsphere reference flow technique was used to measure the regional blood flow of intra- and extracranial tissues. 4. Electrical stimulation of the DFA appeared to increase the regional blood flow of both cerebral hemispheres (intracranial tissues) and to increase predominantly the regional blood flow of extracranial tissues on the side ipsilateral to stimulation. Increases in the regional blood flow of intracranial tissues were enhanced after i.v. administration of atropine but reduced with physostigmine. In contrast, increases in the regional blood flow of extracranial tissues were reduced after i.v. atropine but enhanced after physostigmine. 5. These findings suggest that DFA stimulation may promote the release of ACh in intra- and extracranial vessels. The muscarinic action may restrict the DFA-induced increase in blood flow of intracranial tissues, but enhance that of extracranial tissues.

Distribution of FMRFamide-immunoreactive nerve fibers in the carotid labyrinth of the bullfrog, Rana catesbeiana in corresponding differential interference-contrast (Nomarski) images.

Immunoreactivities for FMRFamide and substance P (SP) in the carotid labyrinth of the bullfrog were detected using the peroxidase-antiperoxidase method, and the results compared with corresponding differential interference-contrast (Nomarski) images. Colocalization of both peptides was determined by the indirect double immunofluorescence method. Immunoreactivities for FMRFamide and SP were found in nerve fibers distributed in the intervascular stroma of the labyrinth. The FMRFamide-immunoreactive fibers were less numerous than the SP-immunoreactive fibers. In the Nomarski image, FMRFamide-fibers were recognized in relief, with most of them located near the walls of blood vessels. All FMRFamide-fibers coexisted with SP. The results suggest that FMRFamide-immunoreactive fibers are also involved in local vascular regulation of the carotid labyrinth.