scholarly journals Testosterone Supplementation Induces Age-Dependent Augmentation of the Hypoxic Ventilatory Response in Male Rats With Contributions From the Carotid Bodies

2021 ◽  
Vol 12 ◽  
Author(s):  
Tara A. Janes ◽  
Danuzia Ambrozio-Marques ◽  
Sébastien Fournier ◽  
Vincent Joseph ◽  
Jorge Soliz ◽  
...  
Keyword(s):  
Carotid Body ◽  
Ex Vivo ◽  
Age Groups ◽  
Free Testosterone ◽  
Male Rats ◽  
Whole Body ◽  
Carotid Bodies ◽  
Age Dependent ◽  
Vehicle Treatment ◽  
Body Responsiveness

Excessive carotid body responsiveness to O2 and/or CO2/H+ stimuli contributes to respiratory instability and apneas during sleep. In hypogonadal men, testosterone supplementation may increase the risk of sleep-disordered breathing; however, the site of action is unknown. The present study tested the hypothesis that testosterone supplementation potentiates carotid body responsiveness to hypoxia in adult male rats. Because testosterone levels decline with age, we also determined whether these effects were age-dependent. In situ hybridization determined that androgen receptor mRNA was present in the carotid bodies and caudal nucleus of the solitary tract of adult (69 days old) and aging (193–206 days old) male rats. In urethane-anesthetized rats injected with testosterone propionate (2 mg/kg; i.p.), peak breathing frequency measured during hypoxia (FiO2 = 0.12) was 11% greater vs. the vehicle treatment group. Interestingly, response intensity following testosterone treatment was positively correlated with animal age. Exposing ex vivo carotid body preparations from young and aging rats to testosterone (5 nM, free testosterone) 90–120 min prior to testing showed that the carotid sinus nerve firing rate during hypoxia (5% CO2 + 95% N2; 15 min) was augmented in both age groups as compared to vehicle (<0.001% DMSO). Ventilatory measurements performed using whole body plethysmography revealed that testosterone supplementation (2 mg/kg; i.p.) 2 h prior reduced apnea frequency during sleep. We conclude that in healthy rats, age-dependent potentiation of the carotid body’s response to hypoxia by acute testosterone supplementation does not favor the occurrence of apneas but rather appears to stabilize breathing during sleep.

Effect of two paradigms of chronic intermittent hypoxia on carotid body sensory activity

2004 ◽  
Vol 96 (3) ◽  
pp. 1236-1242 ◽  
Author(s):  
Ying-Jie Peng ◽  
Nanduri R. Prabhakar
Keyword(s):  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Ex Vivo ◽  
Previous Treatment ◽  
Male Rats ◽  
Sensory Response ◽  
Chronic Intermittent Hypoxia ◽  
Radical Scavenger ◽  
Sprague Dawley ◽  
Carotid Bodies

Reflexes arising from the carotid bodies may play an important role in cardiorespiratory changes evoked by chronic intermittent hypoxia (CIH). In the present study, we examined whether CIH affects the hypoxic sensing ability of the carotid bodies and, if so, by what mechanisms. Experiments were performed on adult male rats (Sprague-Dawley, 250–300 g) exposed to two paradigms of CIH for 10 days: 1) multiple exposures to short durations of intermittent hypoxia per day (SDIH; 15sof5%O2 + 5 min of 21% O2, 9 episodes/h, 8 h/day) and 2) single exposure to longer durations of intermittent hypoxia per day [LDIH; 4 h of hypobaric hypoxia (0.4 atm/day) + 20 h of normoxia]. Carotid body sensory response to graded isocapnic hypoxia was examined in both groups of animals under anesthetized conditions. Hypoxic sensory response was significantly enhanced in SDIH but not in LDIH animals. Similar enhancement in hypoxic sensory response was also elicited in ex vivo carotid bodies from SDIH animals, suggesting that the effects were not secondary to cardiovascular changes. SDIH, however, had no significant effect on the hypercapnic sensory response. The effects of SDIH on the hypoxic sensory response completely reversed after SDIH animals were placed in a normoxic environment for an additional 10 days. Previous treatment with systemic administration of [Formula: see text] radical scavenger prevented SDIH-induced augmentation of the hypoxic sensory response. These results demonstrate that SDIH but not LDIH results in selective augmentation of the hypoxic response of the carotid body and [Formula: see text] radicals play an important role in SDIH-induced sensitization of the carotid body.

Changes in breathing pattern mediated by intrapulmonary CO2 receptors in chickens

1982 ◽  
Vol 52 (1) ◽  
pp. 162-167 ◽  
Author(s):  
R. D. Tallman ◽  
A. L. Kunz
Keyword(s):  
Carotid Body ◽  
Breathing Pattern ◽  
Complete Removal ◽  
Whole Body ◽  
Fixed Duration ◽  
Experimental Protocol ◽  
Phase Switching ◽  
Carotid Chemoreceptors ◽  
Carotid Bodies ◽  
Body Plethysmograph

The ventilation of unanesthetized tracheostomized chickens was measured using a whole-body plethysmograph. The inspired CO2 fraction was quickly manipulated between 0.05 and 0.0 in such a way as to limit the fresh air inspired to a fixed duration pulse preceded and followed by 5% CO2. As was previously shown with this experimental protocol [Tallman et al., Am. J. Physiol. 237 (Regulatory Integrative Comp. Physiol. 6): R260–R265, 1979], the duration of inspiration and expiration (TI and TE, respectively) was dependent on the timing, relative to inspiration, that the pulse of air arrived at the lung. To study the possible involvement of arterial chemoreceptors in this reflex, a method of denervating the carotid chemoreceptors in this reflex, a method of denervating the carotid bodies was developed. After denervation, the hyperpneic response to intravenous NaCN and 2–3 breaths of N2 was eliminated, indicating the complete removal of arterial chemoreflexes. When tested with the same protocol of CO2 inhalation following carotid body denervation, TI and TE were still dependent on the delay of the fresh air pulse. These experiments support the conclusion that intrapulmonary CO2 receptors (IPC) mediate the reflexes studied and provide evidence that IPC affect the phase-switching mechanisms on a breath-to-breath basis.

scholarly journals Comparative analysis of neonatal and adult rat carotid body responses to chronic intermittent hypoxia

2008 ◽  
Vol 104 (5) ◽  
pp. 1287-1294 ◽  
Author(s):  
Anita Pawar ◽  
Ying-Jie Peng ◽  
Frank J. Jacono ◽  
Nanduri R. Prabhakar
Keyword(s):  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Ex Vivo ◽  
Adult Life ◽  
Sensory Response ◽  
Chronic Intermittent Hypoxia ◽  
Adult Rats ◽  
Adult Rat ◽  
Carotid Bodies

Previous studies suggest that carotid body responses to long-term changes in environmental oxygen differ between neonates and adults. In the present study we tested the hypothesis that the effects of chronic intermittent hypoxia (CIH) on the carotid body differ between neonates and adult rats. Experiments were performed on neonatal (1–10 days) and adult (6–8 wk) males exposed either to CIH (9 episodes/h; 8 h/day) or to normoxia. Sensory activity was recorded from ex vivo carotid bodies. CIH augmented the hypoxic sensory response (HSR) in both groups. The magnitude of CIH-evoked hypoxic sensitization was significantly greater in neonates than in adults. Seventy-two episodes of CIH were sufficient to evoke hypoxic sensitization in neonates, whereas as many as 720 CIH episodes were required in adults, suggesting that neonatal carotid bodies are more sensitive to CIH than adult carotid bodies. CIH-induced hypoxic sensitization was reversed in adult rats after reexposure to 10 days of normoxia, whereas the effects of neonatal CIH persisted into adult life (2 mo). Acute intermittent hypoxia (IH) evoked sensory long-term facilitation of the carotid body activity (sensory LTF, i.e., increased baseline neural activity following acute IH) in CIH-exposed adults but not in neonates. The effects of CIH were associated with hyperplasia of glomus cells in neonatal but not in adult carotid bodies. These observations demonstrate that responses to CIH differ between neonates and adults with regard to the magnitude of sensitization of HSR, susceptibility to CIH, induction of sensory LTF, reversibility of the responses, and morphological remodeling of the chemoreceptor tissue.

Role of the carotid bodies in chemosensory ventilatory responses in the anesthetized mouse

2004 ◽  
Vol 97 (4) ◽  
pp. 1401-1407 ◽  
Author(s):  
Masahiko Izumizaki ◽  
Mieczyslaw Pokorski ◽  
Ikuo Homma
Keyword(s):  
Tidal Volume ◽  
Carotid Body ◽  
Minute Ventilation ◽  
Respiratory Frequency ◽  
Whole Body ◽  
Sudden Increase ◽  
Ventilatory Responses ◽  
Carotid Bodies ◽  
Before And After ◽  
Carotid Body Denervation

We examined the effects of carotid body denervation on ventilatory responses to normoxia (21% O2 in N2 for 240 s), hypoxic hypoxia (10 and 15% O2 in N2 for 90 and 120 s, respectively), and hyperoxic hypercapnia (5% CO2 in O2 for 240 s) in the spontaneously breathing urethane-anesthetized mouse. Respiratory measurements were made with a whole body, single-chamber plethysmograph before and after cutting both carotid sinus nerves. Baseline measurements in air showed that carotid body denervation was accompanied by lower minute ventilation with a reduction in respiratory frequency. On the basis of measurements with an open-circuit system, no significant differences in O2 consumption or CO2 production before and after chemodenervation were found. During both levels of hypoxia, animals with intact sinus nerves had increased respiratory frequency, tidal volume, and minute ventilation; however, after chemodenervation, animals experienced a drop in respiratory frequency and ventilatory depression. Tidal volume responses during 15% hypoxia were similar before and after carotid body denervation; during 10% hypoxia in chemodenervated animals, there was a sudden increase in tidal volume with an increase in the rate of inspiration, suggesting that gasping occurred. During hyperoxic hypercapnia, ventilatory responses were lower with a smaller tidal volume after chemodenervation than before. We conclude that the carotid bodies are essential for maintaining ventilation during eupnea, hypoxia, and hypercapnia in the anesthetized mouse.

scholarly journals Mitochondrial Succinate Metabolism and Reactive Oxygen Species Are Important but Not Essential for Eliciting Carotid Body and Ventilatory Responses to Hypoxia in the Rat

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 840
Author(s):  
Agnieszka Swiderska ◽  
Andrew M. Coney ◽  
Abdulaziz A. Alzahrani ◽  
Hayyaf S. Aldossary ◽  
Nikolaos Batis ◽  
...  
Keyword(s):  
Carotid Body ◽  
Ex Vivo ◽  
Acute Hypoxia ◽  
Whole Body ◽  
Dimethyl Malonate ◽  
Peripheral Chemoreceptor ◽  
Ventilatory Responses ◽  
Mitochondrial Ros ◽  
O2 Sensing

Reflex increases in breathing in response to acute hypoxia are dependent on activation of the carotid body (CB)—A specialised peripheral chemoreceptor. Central to CB O2-sensing is their unique mitochondria but the link between mitochondrial inhibition and cellular stimulation is unresolved. The objective of this study was to evaluate if ex vivo intact CB nerve activity and in vivo whole body ventilatory responses to hypoxia were modified by alterations in succinate metabolism and mitochondrial ROS (mitoROS) generation in the rat. Application of diethyl succinate (DESucc) caused concentration-dependent increases in chemoafferent frequency measuring approximately 10–30% of that induced by severe hypoxia. Inhibition of mitochondrial succinate metabolism by dimethyl malonate (DMM) evoked basal excitation and attenuated the rise in chemoafferent activity in hypoxia. However, approximately 50% of the response to hypoxia was preserved. MitoTEMPO (MitoT) and 10-(6′-plastoquinonyl) decyltriphenylphosphonium (SKQ1) (mitochondrial antioxidants) decreased chemoafferent activity in hypoxia by approximately 20–50%. In awake animals, MitoT and SKQ1 attenuated the rise in respiratory frequency during hypoxia, and SKQ1 also significantly blunted the overall hypoxic ventilatory response (HVR) by approximately 20%. Thus, whilst the data support a role for succinate and mitoROS in CB and whole body O2-sensing in the rat, they are not the sole mediators. Treatment of the CB with mitochondrial selective antioxidants may offer a new approach for treating CB-related cardiovascular–respiratory disorders.

Anandamide modulates carotid sinus nerve afferent activity via TRPV1 receptors increasing responses to heat

2012 ◽  
Vol 112 (1) ◽  
pp. 212-224 ◽  
Author(s):  
Arijit Roy ◽  
Sravan Mandadi ◽  
Marie-Noelle Fiamma ◽  
Ekaterina Rodikova ◽  
Erin V. Ferguson ◽  
...  
Keyword(s):  
Carotid Body ◽  
Carotid Sinus ◽  
Ex Vivo ◽  
Null Mouse ◽  
Temperature Sensitive ◽  
Carotid Sinus Nerve ◽  
Afferent Activity ◽  
Mild Hyperthermia ◽  
Carotid Bodies ◽  
Trpv1 Receptors

Abnormal respiratory chemosensitivity is implicated in recurrent apnea syndromes, with the peripheral chemoreceptors, the carotid bodies, playing a particularly important role. Previous work suggests that supraphysiological concentrations of the endocannabinoid endovanilloid and TASK channel blocker anandamide (ANA) excite carotid bodies, but the mechanism(s) and physiological significance are unknown. Given that carotid body output is temperature-sensitive, we hypothesized that ANA stimulates carotid body chemosensory afferents via temperature-sensitive vanilloid (TRPV1) receptors. To test this hypothesis, we used the dual-perfused in situ rat preparation to confirm that independent perfusion of carotid arteries with supraphysiological concentrations of ANA strongly excites carotid sinus nerve afferents and that this activity is sufficient to increase phrenic activity. Next, using ex vivo carotid body preparations, we demonstrate that these effects are mediated by TRPV1 receptors, not CB1 receptors or TASK channels: in CB1-null mouse preparations, ANA increased afferent activity across all levels of Po2, whereas in TRPV1-null mouse preparations, the stimulatory effect of ANA was absent. In rat ex vivo preparations, ANA's stimulatory effects were mimicked by olvanil, a nonpungent TRPV1 agonist, and suppressed by the TRPV1 antagonist AMG-9810. The specific CB1 agonist oleamide had no effect. Physiological levels of ANA had no effect alone but increased sensitivity to mild hyperthermia. AMG-9810 blocked ANA's effect on the temperature response. Immunolabeling and RT-PCR demonstrated that TRPV1 receptors are not expressed in carotid body glomus cells but reside in petrosal sensory afferents. Together, these results suggest that ANA plays a physiological role in augmenting afferent responses to mild hyperthermia by activating TRPV1 receptors on petrosal afferents.

Acetylcholine release from the carotid body by hypoxia: evidence for the involvement of autoinhibitory receptors

2004 ◽  
Vol 96 (1) ◽  
pp. 376-383 ◽  
Author(s):  
Dong-Kyu Kim ◽  
Nanduri R. Prabhakar ◽  
Ganesh K. Kumar
Keyword(s):  
Carotid Body ◽  
Ex Vivo ◽  
Primary Cultures ◽  
Acetylcholinesterase Activity ◽  
Electrochemical Analysis ◽  
Ach Release ◽  
Glomus Cells ◽  
Carotid Bodies ◽  
High K ◽  
Hydrolysis Of

The purpose of the present study was to investigate whether hypoxia influences acetylcholine (ACh) release from the rabbit carotid body and, if so, to determine the mechanism(s) associated with this response. ACh is expressed in the rabbit carotid body (5.6 ± 1.3 pmol/carotid body) as evidenced by electrochemical analysis. Immunocytochemical analysis of the primary cultures of the carotid body with antibody specific to ACh further showed that ACh-like immunoreactivity is localized to many glomus cells. The effect of hypoxia on ACh release was examined in ex vivo carotid bodies harvested from anesthetized rabbits. The basal release of ACh during normoxia (∼150 Torr) averaged 5.9 ± 0.5 fmol·min-1·carotid body-1. Lowering the Po2 to 90 and 20 Torr progressively decreased ACh release by ∼15 and ∼68%, respectively. ACh release returned to the basal value on reoxygenation. Simultaneous monitoring of dopamine showed a sixfold increase in dopamine release during hypoxia. Hypercapnia (21% O2 + 10% CO2) as well as high K+ (100 mM) facilitated ACh release from the carotid body, suggesting that hypoxia-induced inhibition of ACh release is not due to deterioration of the carotid body. Hypoxia had no significant effect on acetylcholinesterase activity in the medium, implying that increased hydrolysis of ACh does not account for hypoxia-induced inhibition of ACh release. In the presence of either atropine (10 μM) or domperidone (10 μM), hypoxia stimulated ACh release. These results demonstrate that glomus cells of the rabbit carotid body express ACh and that hypoxia overall inhibits ACh release via activation of muscarinic and dopaminergic autoinhibitory receptors in the carotid body.

Chronic CO exposure stimulates erythropoiesis but not glomus cell growth

1989 ◽  
Vol 67 (4) ◽  
pp. 1383-1387 ◽  
Author(s):  
A. K. Sherpa ◽  
K. H. Albertine ◽  
D. G. Penney ◽  
B. Thompkins ◽  
S. Lahiri
Keyword(s):  
Blood Flow ◽  
Carotid Body ◽  
Local Effect ◽  
Male Rats ◽  
Capillary Endothelium ◽  
Tissue Blood Flow ◽  
Type I ◽  
Carotid Bodies ◽  
Tissue Po2 ◽  
Significant Difference

The effect of chronic CO exposure, which stimulates erythropoietin production and erythropoiesis, was studied on carotid body cells in the rat. The hypothesis to be tested was that chronic CO inhalation would stimulate cellular hypertrophy and hyperplasia of carotid body if it caused local tissue hypoxia as in chronic hypoxia. The failure of an appropriate response would indicate a lack of a specific local effect on carotid body tissue PO2 presumably because of its unusually high tissue blood flow. Six young male rats were exposed to 0.4–0.5 Torr (0.05–0.07%) inspired PCO in air for 22 days. Control rats (n = 6) were maintained under similar conditions except for CO exposure. After the exposure period the rats were anesthetized, blood was collected for hematocrit, and the carotid bodies were surgically exposed and fixed for electron microscopy and morphometry of type I and type II cells and capillary endothelium. Hematocrit was significantly greater in the CO-exposed group (75 vs. 48%), whereas no significant difference was found in the carotid body parenchyma between the control and CO-exposed groups. We conclude that the lack of an effect of chronic CO exposure on the carotid bodies in contrast to the strong erythropoietic response indicates a relatively high tissue blood flow rate in the carotid body and that CO did not exert a direct cellular effect. The results also suggest that the hypertrophic response of carotid body glomus cells to chronic hypoxic hypoxia is the result of a local direct effect of low PO2 rather than secondary to systemic effects.

Mechanism of changes in hepatic sinusoidal and biliary glutathione efflux with age in rats

1991 ◽  
Vol 261 (4) ◽  
pp. G648-G656
Author(s):  
M. Ookhtens ◽  
T. Maddatu
Keyword(s):  
Membrane Potential ◽  
Reduced Glutathione ◽  
Age Groups ◽  
Kinetic Mechanism ◽  
Female Rats ◽  
Male Rats ◽  
Michaelis Constant ◽  
Appreciable Change ◽  
Age Dependent ◽  
Kinetics Of

To delineate the kinetic mechanism(s) of declining sinusoidal reduced glutathione (GSH) efflux with age, we perfused livers of male rats ages approximately 1-1.5, approximately 2-3, and approximately 3.5-6 mo old and measured sinusoidal and biliary GSH and oxidized glutathione (GSSG) effluxes. Our results showed declining GSH transport to be solely due to a falling maximum transport rate (Vmax) and not an increasing Michaelis constant (Km)(Vmax = 24.2 +/- 2.95, 15.8 +/- 1.51, and 8.61 +/- 0.75 nmol. min-1.g-1; Km = 3.0 +/- 0.42, 2.6 +/- 0.31, and 2.6 +/- 0.43 mumol/g for the three age groups, respectively). Because hepatocyte membrane potential was earlier implicated as a driving force for GSH efflux and hepatocytes of female rats were reported to be less polarized than those of males, we likewise studied the kinetics of sinusoidal GSH efflux from livers of female rats of three age groups comparable to our males. Vmax in females tended to be lower than in males. This was more pronounced in the youngest group but was diminished in the older groups. Vmax was again the only parameter declining with age in the female livers, from 19.1 +/- 2.25 to 15.0 +/- 0.95 and 7.83 +/- 0.99 nmol.min-1.g-1, whereas Km remained unchanged at 3.0 +/- 0.45, 3.1 +/- 0.35, and 3.2 +/- 0.72 mumol/g, respectively. Age-dependent changes in GSH efflux were not due to a changing membrane potential. There was no appreciable change in the paracellular permeability with age either.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic cobalt causes hypertrophy of glomus cells in the rat carotid body

1991 ◽  
Vol 261 (1) ◽  
pp. C102-C105 ◽  
Author(s):  
C. Di Giulio ◽  
P. G. Data ◽  
S. Lahiri
Keyword(s):  
Carotid Body ◽  
Cellular Response ◽  
Male Rats ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Glomus Cells ◽  
Carotid Bodies ◽  
Oxygen Sensitive ◽  
A Site

We tested the hypothesis that chronic cobalt administration would induce carotid body cellular response along with polycythemia as found in chronic hypoxia if common oxygen-sensitive mechanisms were involved in the two instances. Morphometric studies were performed on carotid bodies in male rats that were chronically treated with cobalt chloride (0.17 mumol/kg, ip, daily for 6 wk) and in control rats that received blank saline injections. The rats were anesthetized, blood samples were collected for hematocrit, and the carotid bodies were surgically exposed and were perfused and superfused with the buffered fixative (3% glutaraldehyde plus 1% paraformaldehyde, pH 7.40, 330-340 mosM). The carotid bodies were processed, and ultrathin sections were cut for electron microscopy and morphometry of type I (glomus) and type II cells. Hematocrit increased from 44% in the control to 74% in the cobalt-treated rats, and the mean volume of type I cells increased from 424 to 1,061 microns 3. Type II cells did not show any significant change in size. The results suggest that cobalt stimulated oxygen-sensitive mechanism in the glomus cells of the carotid body and that the glomus cell is a site of oxygen chemosensing.

Sign in / Sign up

Export Citation Format

Share Document