The aim of the present study was to explore the role of group II and III metabotropic glutamate receptors (mGluRs) in carotid body plasticity induced by chronic intermittent hypoxia (CIH) in rats. Sprague Dawley (SD) rats were treated with CIH in Oxycycler A84 hypoxic chamber for 4 weeks, and the tail artery blood pressure was measured at the end of model preparation. RT-qPCR was performed to examine the mRNA expression levels of mGluR2/3/8 in rat carotid body. Carotid sinus nerve activity was detected by ex vivo carotid sinus nerve discharge recording technique, and acute intermittent hypoxia (AIH) was administered to induce carotid body sensory long-term facilitation (sLTF), in order to observe the role of group II and group III mGluRs in carotid body plasticity induced by CIH. The results showed that: 1) After 4 weeks of CIH exposure, the blood pressure of rats increased significantly; 2) CIH down-regulated the mRNA levels of mGluR2/3, and up-regulated the mRNA level of mGluR8 in the carotid body; 3) AIH induced sLTF in carotid body of CIH group. In the CIH group, activation of group II mGluRs had no effect on sLTF of carotid body, while activation of group III mGluRs completely inhibited sLTF. These results suggest that CIH increases blood pressure in rats, and group III mGluRs play an inhibitory role in CIH-induced carotid body plasticity in rats.
Rats ; Animals ; Carotid Body/metabolism* ; Rats, Sprague-Dawley ; Hypoxia ; Receptors, Metabotropic Glutamate/metabolism* ; RNA, Messenger/metabolism*

The purpose of the present study was to explore the role of carotid body metabotropic glutamate receptor 1 (mGluR1) in chronic intermittent hypoxia (CIH)-induced carotid body plasticity. Sprague Dawley (SD) rats were exposed to CIH (6%-21% O₂, 4 min/cycle, 8 h/day) for 4 weeks. The blood pressure of rats was monitored non-invasively by tail-cuff method under consciousness. RT-qPCR was used to examine the mRNA expression level of mGluR1 in rat carotid body. Western blot was used to detect the protein expression level of mGluR1 in rat carotid body. The role of mGluR1 in CIH-induced carotid body sensory long-term facilitation (sLTF) was investigated by ex vivo carotid sinus nerve discharge recording, and the carotid body sLTF was evoked by a 10-episode of repetitive acute intermittent hypoxia (AIH: 1 min of 5% O₂ interspersed with 5 min of 95% O₂). The results showed that: 1) CIH increased the systolic blood pressure (P < 0.001), diastolic blood pressure (P < 0.005) and mean arterial blood pressure (P < 0.001) of rats; 2) CIH decreased the mRNA and protein levels of mGluR1 in the rat carotid body (P < 0.01); 3) 4 weeks of CIH induced carotid body sLTF significantly, exhibiting as an increasing baseline sensory activity during post-AIH, which was inhibited by application of an agonist of group I metabotropic glutamate receptors, (S)-3,5-dihydroxyphenylglycine (DHPG), during sLTF induction (P < 0.005). In summary, these results suggest that activation of mGluR1 inhibits CIH-induced carotid body plasticity in rats.
Rats ; Animals ; Carotid Body/metabolism* ; Rats, Sprague-Dawley ; Hypoxia ; Receptors, Metabotropic Glutamate/metabolism* ; RNA, Messenger/metabolism*

To observe the effects of heterograft of glomus cells of carotid body on hemiparkinsonian rat models, rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the right dopaminergic neurons of substantia nigra received intrastriatal glomus cells heterograft. Apomorphine-induced rotation was monitored for 30 min at various time points after grafting. The striata were cut and examined for dopamine content by HPLC and for immunohistochemical staining of tyrosine hydroxylase positive neurons (TH+) at the end of the experiments. The results showed that apomorphine-induced rotational behavior was significantly reduced for 12 weeks and the dopamine contents were significantly elevated after grafting (P < 0.01), and TH+ cells survived better. The present study demonstrates that intrastriatal heterograft of glomus cells within carotid body in rats with 6-OHDA-elicited lesions could reduce apomorphine-induced rotational behavior and elevate the dopamine contents and numbers of TH+ cell surviving within striatum, and can serve as a new and effective alternative for Parkinson disease.
Carotid Body/*cytology ; Carotid Body/transplantation ; *Cell Transplantation ; Dopamine/*metabolism ; Neurons/metabolism ; Parkinson Disease/metabolism ; Parkinson Disease/*surgery ; Random Allocation ; Rats, Sprague-Dawley ; Stereotaxic Techniques ; Transplantation, Heterologous

The experiments were carried out to test whether acid-sensing ion channel 1a and 3 (ASIC1a and ASIC3) were expressed on the primarily cultured type I cells of rat carotid bodies (CBs) and whether the expression of the channels was affected by acid stimulation. The Sprague-Dawley rats of either sex (50-100 g) were used. The CBs were isolated and primarily cultured. The immunofluorescent technique was used to detect the expression of tyrosine hydroxylase (TH), a specific marker of type I cells, in order to identify the type of the cultured cells. The double-label immunofluorescent technique was used to detect the expression of ASIC1a and ASIC3 on the TH-positive type I cells. To detect the influence of acid stimulation on the expressions of ASIC1a and ASIC3, each batch of primarily cultured cells were randomly divided into pH7.3 group (control group), pH6.8 group and pH6.2 group (n=9 in each group). The cells in above three groups were treated with pH7.3, pH6.8 and pH6.2 mediums for 24 h, respectively, and then the mRNA expressions of ASIC1a and ASIC3 in type I cells were detected by semi-quantitative RT-PCR technique. The results showed that more than 93% of the primarily cultured CB cells were TH-positive, indicating that most of the cultured cells were type I cells. Furthermore, all TH-positive cells expressed ASIC1a or ASIC3. After the cells were treated with acid stimulation, the amount of ASIC1a mRNA did not change significantly (P>0.05 vs control group); the amount of ASIC3 mRNA had no significant change in pH6.8 group compared with that in control group, but decreased significantly in pH6.2 group (P<0.01 vs control group, P<0.05 vs pH6.8 group). It is concluded that acid stimulation down-regulates the level of ASIC3 mRNA, but has no effect on the level of ASIC1a mRNA.
Acid Sensing Ion Channels ; metabolism ; Acids ; pharmacology ; Animals ; Carotid Body ; cytology ; metabolism ; Cells, Cultured ; Female ; Male ; Rats ; Rats, Sprague-Dawley

The carotid body can transduce hypoxia and other blood-borne stimuli, perhaps including hypoglycaemia, into afferent neural discharge that is graded for intensity and which forms the afferent limb of a cardiorespiratory and neuroendocrine reflex loop. Hypoxia inhibits a variety of K(+) channels in the type I cells of the carotid body, in a seemingly species-dependent manner, and the resultant membrane depolarisation is sufficient to activate voltage-gated Ca(2+) entry leading to neurosecretion and afferent discharge. The ion channels that respond to hypoxia appear to do so indirectly and recent work has therefore focussed upon identification of other proteins in the type I cells of the carotid body that may play key roles in the oxygen sensing process. Whilst a role for mitochondrial and/or NADPH-derived reactive oxygen species (ROS) has been proposed, the evidence for their signalling hypoxia in the carotid body is presently less than compelling and two alternate hypotheses are currently being tested further. The first implicates haemoxygenase 2 (HO-2), which may control specific K(+) channel activation through O(2)-dependent production of the signalling molecule, carbon monoxide. The second hypothesis suggests a role for the cellular energy sensor, AMP-activated protein kinase (AMPK), which can inhibit type I cell K(+) channels and increase afferent discharge when activated by hypoxia-induced elevations in the AMP: ATP ratio. The apparent richness of O(2)-sensitive K(+) channels and sensor mechanisms within this organ may indicate a redundancy system for this vital cellular process or it may be that each protein contributes differently to the overall response, for example, with different O(2) affinities. The mechanism by which low glucose is sensed is not yet known, but recent evidence suggests that it is not via closure of K(+) channels, unlike the hypoxia transduction process.
AMP-Activated Protein Kinases ; metabolism ; Animals ; Carotid Body ; physiology ; Chemoreceptor Cells ; physiology ; Heme Oxygenase (Decyclizing) ; metabolism ; Humans ; Hypoxia ; physiopathology ; Potassium Channels ; metabolism ; Reactive Oxygen Species ; metabolism

To observe the effects of heterograft of glomus cells of carotid body on hemiparkinsonian rat models, rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the right dopaminergic neurons of substantia nigra received intrastriatal glomus cells heterograft. Apomorphine-induced rotation was monitored for 30 min at various time points after grafting. The striata were cut and examined for dopamine content by HPLC and for immunohistochemical staining of tyrosine hydroxylase positive neurons (TH+) at the end of the experiments. The results showed that apomorphine-induced rotational behavior was significantly reduced for 12 weeks and the dopamine contents were significantly elevated after grafting (P < 0.01), and TH+ cells survived better. The present study demonstrates that intrastriatal heterograft of glomus cells within carotid body in rats with 6-OHDA-elicited lesions could reduce apomorphine-induced rotational behavior and elevate the dopamine contents and numbers of TH+ cell surviving within striatum, and can serve as a new and effective alternative for Parkinson disease.
Animals ; Carotid Body ; cytology ; transplantation ; Cell Transplantation ; Dopamine ; metabolism ; Female ; Neurons ; metabolism ; Parkinson Disease ; metabolism ; surgery ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stereotaxic Techniques ; Transplantation, Heterologous

PURPOSE: The purpose of this study was to investigate the effects of 12 weeks of combined exercise on vascular function-related inflammation, carotid intima-media thickness and fitness factors in obese middle-aged women with metabolic syndrome.METHODS: The subjects of this study were 40 middle-aged women in their 40s with metabolic syndrome but no specific disease. The exercise group performed aerobic exercise and resistance exercise five times a week for 12 weeks, and then measured body composition, blood pressure, vascular function-related inflammation factors, metabolic syndrome factors, carotid intima-media thickness, and physical factors.RESULTS: The exercise group showed a significant (p<0.05) reduction after exercise in all items related to body composition, systolic and diastolic blood pressure, and intima-media thickness of the right carotid and left carotid arteries. Exercise group showed a significant decrease (p<0.05) after exercise in interleukin-6, tumor necrosis factor-α, leptin, and all items of glucose metabolism-related variables. The exercise group showed a significant (p<0.05) increase after exercise physical efficiency index, grip strength, sit-ups, and sit & reach. After 12 weeks of exercise training, the reduction of intima-media thickness of the carotid artery was significantly (p<0.05) correlated with the improvement of body weight, systolic and diastolic blood pressure, grip and sit & reach, blood HbA1c, and triglyceride concentration.CONCLUSION: In conclusion, metabolic syndrome improved the body composition, blood glucose metabolism and lipid variables after 12 weeks of combined exercise program for obese middle-aged women. Significant improvement in blood pressure and carotid endometrial thickness, which is a function-related indicator, was confirmed.
Blood Glucose ; Blood Pressure ; Body Composition ; Body Weight ; Carotid Arteries ; Carotid Intima-Media Thickness ; Exercise ; Female ; Glucose ; Hand Strength ; Humans ; Inflammation ; Interleukin-6 ; Leptin ; Metabolism ; Necrosis ; Physical Fitness ; Triglycerides

The effects of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin on the enhanced hypoxia induced factor-1α (HIF-1α) and endothelin-1 (ET-1) expression, elevated systolic blood pressure under chronic intermittent hypoxia (CIH) condition and its action mechanism were investigated. Thirty healthy 8-week old Sprague-Dawley (SD) male rats were randomly divided into three groups (n=10 each): sham group, CIH group, and apocynin-treated CIH group. Tail artery systolic blood pressure was measured by tail-cuff method. Real-time fluorescence quantitative polymerase chain reaction (PCR) was used to detect the mRNA expression of HIF-1α and ET-1 in the carotid body, and the HIF-1α protein expression was examined by using Western blotting. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined by using colorimetric method. In addition, the plasma ET-1 and HIF-1α levels were measured by using enzyme-linked immunosorbent assay. It was found that CIH exposure was associated with increased MDA levels, and apocynin-treated CIH animals showed reduction in MDA levels. Apocynin treatment prevented CIH-induced hypertension as well as CIH-induced decrease in SOD. The increases of HIF-1α and ET-1 mRNA along with HIF-1α protein expression in the carotid body, and elevated circulating HIF-1α and ET-1 levels were observed in CIH-exposed animals. Treatment with apocynin significantly decreased the ET-1 mRNA, HIF-1α protein expression and circulating HIF-1α level in CIH-exposed animals, and there was no statistically significant difference in the HIF-1α mRNA expression between CIH group and apocynin-treated group. These results indicated that apocynin alleviated CIH-induced hypertension by inhibiting NADPH oxidase, further leading to the reduced vasoconstrictor ET-1 level and oxidative stress. HIF-1α/ET-1 system signal pathway may interact with CIH-induced NADPH oxidase-dependent oxidative stress. Inhibition of NADPH oxidase activity may hopefully serve as a useful strategy for prevention and treatment of obstructive sleep apnea hypopnea syndrome-induced hypertension.
Acetophenones ; administration & dosage ; Animals ; Antioxidants ; administration & dosage ; Carotid Body ; drug effects ; metabolism ; Endothelin-1 ; metabolism ; Hypoxia ; drug therapy ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; NADP ; antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Treatment Outcome

To investigate the changes in the expression of basic fibroblast growth factor (bFGF) and transforming growth factor beta 2 (TGFbeta2) in glomus cell grafts of carotid body in the rat model of 6-hydroxydopamine-induced Parkinson disease, immunohistochemical staining of bFGF and TGFbeta2 in the sections of striate body was done on the 2nd, 4th and 12th week after transplantation. The results showed that on the 2nd week after transplantation, bFGF and TGFbeta2 were not detectable in the glumous cell grafts. On the 4th week after graft, bFGF and TGFbeta2 immunoreactivity was increased within the grafts and at the graft-host interface but was restricted only to astrocytes. In the striatum surrounding the graft, bFGF was expressed persistently, while TGFbeta2 showed transient expression. It was suggested that the transient expression of TGFbeta2 was likely due more to the trauma imposed by the graft procedure than to an intrinsic. The deficiency in astrocytic bFGF early after graft may be responsible for the poor survival of grafted glomus cells of carotid body.
Animals ; Carotid Body ; cytology ; transplantation ; Female ; Fibroblast Growth Factor 2 ; biosynthesis ; genetics ; Hydroxydopamines ; Parkinson Disease ; etiology ; metabolism ; surgery ; Rats ; Transforming Growth Factor beta ; biosynthesis ; genetics ; Transforming Growth Factor beta2 ; Transplantation, Homologous

Atherosclerotic cardiovascular disease(AVD) is a major cause of the mortality and morbidity in end-stage renal disease(ESRD) patients undergoing chronic dialysis therapy. The factors such as lipopretein metabolism abnormality, diabetes, hypertension, hyperhomocysteinemia and oxidative stress have been implicated as underlying causes related AVD. Malnutrition, chronic inflammation, increased oxidative stress, hyperparathyroidism and its related lipoprotein abnormalities are suggested to accelerate AVD in ESRD patients. High-resolution B-mode ultrasono-graphy has been used to evaluate atherosclerotic change in carotid artery in a number of epidemiologic or clinical studies because of its non-invasive advantage and proven effects in predicting AVD or cardiovascular mortality. Using high-resolution B-mode sonography, we evaluated the presence of plaque and carotid intima-media area(cIM area), which is known to be a good predictor of athero-sclerosis. We compared and analyzed those sonographic findings according to a number of selected clinical and laboratory factors. Study subjects were 27 stable ESRD patient receiving hemodialysis(HD) or chronic ambulatory peritoneal dialysis(CAPD) at least over 24 months. The patients with present or past coronary, cerebral or peripheral vascular disease, history of anti-platelet agents or age over 70 years were excluded. Nine HD and 18 CAPD patients were included and mean age was 52.1+/-2.6 years and number of male and female patients were sixteen and eleven. Among many factors, sex, age, dialysis duration, diabetes, smoking history, blood pressure, body mass index, albumin, creatinine, high-density lipoprotein, triglyceride, C-reactive protein, total calcium, phosphorus, intact-parathyroidid hormone were selected and analyzed for their correlation with carotid sonograpic findings. 1) Mean cIM area of all patients was 15.4+/-0.7 mm2. cIM area was significantly increased in CAPD patients compared to HD patients(16.5+/-1.2 vs 14.9+/- 0.9mm2, p<0.05). Atherosclerotic plaques were found in 48.1% and bilateral lesion was found in 18.5% of all patients. The incidence of the plaque was 42.1% in HD and 55.6% in CAPD patients. 2) cIM area was more significantly increased in male than female(16.7+/-0.8 vs 13.6+/-1.2mm2, in diabetes than non-diabetes(16.4+/-0.8 vs 14.7+/-l.lmm2) and in smoker than non-smoker(18.8+/-0.7 vs 12.8+/-0.7mm2, p<0.05). It was also significantly inereased in patients with body mass index more than 2.3kg/ m(18.3+/-1.1 vs 14.6+/-0.8mm), systolic blood pres-sure more than 14mmHg(16.6+/-0.7 vs 13.0+/-1.2mm) and C-reactive pretein more than 0.5 mg/dL(18.9+/-1.5 vs 14.2+/-0.77mm2p<0.05). Among those factors, age, systolic blood pressure, body mass index and C-reactive protein were proven to positively correlate to cIM area with statistical significance(p<0.05). Even though cIM area was increased in patients with high serum parathyroid hormone, high total cholesterol and triglyceride and low high-density lipoprotein level, no statistical significances were found in these factors. 3) In comparison of each factor according to the presence of the plaque, age and the presence of diabetes were proven to be significantly different between patients without the plaque and with the plaque(45.7+/-2.7 vs 59.5+/-3.8 year, 33.3% vs 53.8%, respectively, p<0.05). Systolic blood pressure and C-reactive protein were increased in patients with the plaque but no statistical significance was shown. In conclusions, we found that old age, male sex, presence of diabetes, smoking history, high systolic blood pressure, increased body mass index and increased C-reactive protein were significantly related to increased cIM area and the plaque was more frequent in old age and diabetes patients using high resolution B-mode ultrasonography. It can be assumed that inflammatory state as reflected by C-reactive protein would be more related with atherosclerosis in ESRD patients than such as nutritional state, parathyroid hormone or lipoprotein metabolism based on these results. Fusing prospective analysis demonstrating causeeffect relationship or analyzing inflammatory index such as TNF-a or interleukin would be necessary to prove this assumption.
Age Factors ; Atherosclerosis* ; Blood Pressure ; Body Mass Index ; C-Reactive Protein ; Calcium ; Carotid Arteries* ; Cholesterol ; Creatinine ; Dialysis ; Female ; Humans ; Hyperhomocysteinemia ; Hyperparathyroidism ; Hypertension ; Incidence ; Inflammation ; Interleukins ; Kidney Failure, Chronic* ; Lipoproteins ; Male ; Malnutrition ; Metabolism ; Mortality ; Oxidative Stress ; Parathyroid Hormone ; Peripheral Vascular Diseases ; Peritoneal Dialysis, Continuous Ambulatory ; Phosphorus ; Plaque, Atherosclerotic ; Sex Factors ; Smoke ; Smoking ; Triglycerides ; Ultrasonography*