Species differences in respiratory rhythm generation in rodents

2010 ◽  
Vol 298 (4) ◽  
pp. R887-R898 ◽  
Author(s):  
B. M. Gajda ◽  
A. Y. Fong ◽  
W. K. Milsom
Keyword(s):  
Respiratory Rhythm ◽  
Inhibitory Effect ◽  
Motor Output ◽  
Flufenamic Acid ◽  
Respiratory Drive ◽  
Respiratory Rhythmogenesis ◽  
Young Rats ◽  
Highly Sensitive

We examined the role of riluzole (RIL)- and flufenamic acid (FFA)-sensitive mechanisms in respiratory rhythmogenesis in rats and hamsters using the in situ arterially perfused preparation. Based on the hypothesis that respiratory networks in animals capable of autoresuscitation would have a greater prevalence of membrane mechanisms that promote endogenous bursting, we predicted that older (weaned) hamsters (a hibernating species) would be more sensitive to the blockade of RIL- and FFA-sensitive mechanisms than age-matched rats and that younger (preweaned) rats would behave more like hamsters. Consistent with this, we found that respiratory motor output in weaned hamsters [>21 days postnatal (P21)] was highly sensitive to RIL (0.2–20 μM), while in young rats (P12–14) it was less so (only affected at higher concentrations of RIL), and weaned rats were not affected at all. On the other hand, respiratory motor output was equally reduced by FFA (0.25–25 μM) in both young and weaned rats but was unaffected in weaned hamsters. Coapplication of RIL and FFA (RIL + FFA) produced greater inhibition of respiration in both young and weaned rats compared with either drug alone. In contrast, in weaned hamsters, FFA coapplication offset the inhibitory effect of RIL alone. Increasing respiratory drive with hypercapnia/acidosis ameliorated the respiratory inhibition produced by RIL + FFA in weaned rats but had no effect in young rats. Data from the present study indicate that respiratory rhythmogenesis in young rats is more dependent on excitatory RIL-sensitive and FFA-sensitive mechanisms than older rats and that fundamental differences exist in the respiratory rhythmogenic mechanisms between rats and hamsters.

Effects on respiratory pattern of focal cooling in the medulla of the dog

1988 ◽  
Vol 65 (5) ◽  
pp. 2004-2010 ◽  
Author(s):  
M. Adams ◽  
T. Chonan ◽  
N. S. Cherniack ◽  
C. von Euler
Keyword(s):  
Respiratory Rhythm ◽  
Nucleus Ambiguus ◽  
Respiratory Pattern ◽  
Respiratory Drive ◽  
Timing Effect ◽  
Diaphragm Electrical Activity ◽  
Inspiratory Activity ◽  
Ventral Medullary Surface ◽  
Focal Cooling

Studies in cats have shown that, in addition to respiratory neuron groups in the dorsomedial (DRG) and ventrolateral (VRG) medulla, neural structures in the most ventral medullary regions are important for the maintenance of respiratory rhythm. The purpose of this study was to determine whether a similar superficially located ventral region was present in the dog and to assess the role of each of the other regions in the canine medulla important in the control of breathing, in 20 anesthetized, vagotomized, and artificially ventilated dogs, a cryoprobe was used to cool selected regions of the medulla to 15-20 degrees C. Respiratory output was determined from phrenic nerve or diaphragm electrical activity. Cooling in or near the nucleus of the solitary tract altered timing and produced little change in the amplitude or rate of rise of inspiratory activity; lengthening of inspiratory time was the most common timing effect observed. Cooling in ventrolateral regions affected the amplitude and rate of rise of respiratory activity. Depression of neural tidal volume and apnea could be produced by unilateral cooling in two ventrolateral regions: 1) near the nucleus ambiguus and nucleus para-ambiguus and 2) just beneath the ventral medullary surface. These findings indicate that in the dog dorsomedial neural structures influence respiratory timing, whereas more ventral structures are important to respiratory drive.

scholarly journals Hering-Breuer Reflex and pre-Botzinger Complex: A Literature Survey

1970 ◽  
Vol 2 ◽  
pp. 89-94
Author(s):  
M Ahmed
Keyword(s):  
Human Subjects ◽  
Respiratory Rhythm ◽  
Physiological Role ◽  
Personal Communication ◽  
In Vivo Studies ◽  
Respiratory Rhythmogenesis ◽  
Neuronal Regulation ◽  
Bötzinger Complex

The existence and physiological role of Hering-Breuer reflex and pre-Botzinger complex has long been depreciated by the Bangladesh society of physiologist (personal communication). The aim of this mini review is to highlight the recent findings on the aforementioned topics. Due to the difficulties in vivo studies in human subjects, many aspects of the neuronal regulation of the respiratory rhythm are still unclear. However, the recent localization of the pre-Botzinger complex in humans and advances in technologies necessitates further exploration of the neuronal circuits in the pre-BotC complex which will subsequently unwrap the magical box and pave the way to solve the puzzle of the mechanism of respiratory rhythmogenesis and its modulation in different pathophysiological conditions. Key Words: Physiology; Hering-Breuer reflex; pre-Botzinger complex; Rhythmic respiration  DOI:10.3329/jbsp.v2i0.988 J Bangladesh Soc Physiol. 2007 Dec;(2):89-94.  

Role of gastric blood flow in impaired defense and repair of aged rat stomachs

1995 ◽  
Vol 269 (5) ◽  
pp. G737-G744 ◽  
Author(s):  
J. E. Gronbech ◽  
E. R. Lacy
Keyword(s):  
Blood Flow ◽  
Mucosal Injury ◽  
Nerve Fibers ◽  
Gastric Blood Flow ◽  
Aged Rats ◽  
Young Rats ◽  
Calcitonin Gene ◽  
Hyperemic Response

To study impaired gastric mucosal tolerance against noxious agents in aged rats, possible factors underlying this observation were compared in anesthetized Fisher 344 young and aged rats. The gastric mucosa was damaged by in situ exposure to 80% ethanol for 30-45 s and by 1 M NaCl for 10 min followed by saline (pH = 1.0) for 60 min in chambered stomachs. The lesion area was significantly larger and epithelial restitution was significantly slower in aged than in young rats after both types of injury. Changes in gastric blood flow were monitored by laser-Doppler velocimetry. Young, but not aged, rats showed a marked increase in gastric blood flow in response to 1 M NaCl, acid challenge, and 640 microM capsaicin for 60 min. Young rats showed a higher density of calcitonin gene-related peptide (CGRP)-staining nerve fibers around submucosal blood vessels and higher mucosal release of prostaglandin E2 and leukotriene C4 than did aged rats. These data suggest that impaired mucosal defense and reduced restitution in aged rats is related to lack of hyperemic response caused by mucosal injury and H+ back-diffusion, which is probably due to decreased density of CGRP-staining nerve fibers and prostaglandin biosynthetic capacity in the mucosa.

scholarly journals Steroidal ferrocenes as potential enzyme inhibitors of the estrogen biosynthesis

2020 ◽  
Vol 71 (3) ◽  
pp. 249-264
Author(s):  
Bianka Edina Herman ◽  
János Gardi ◽  
János Julesz ◽  
Csaba Tömböly ◽  
Eszter Szánti-Pintér ◽  
...  
Keyword(s):  
Enzyme Inhibitors ◽  
Inhibitory Effect ◽  
Ferrocene Derivatives ◽  
17Β Estradiol ◽  
Inhibitory Potential ◽  
Estrogen Biosynthesis

Abstract The potential inhibitory effect of diverse triazolyl-ferrocene steroids on key enzymes of the estrogen biosynthesis was investigated. Test compounds were synthesized via copper-catalyzed cycloaddition of steroidal azides and ferrocenyl-alkynes using our efficient methodology published previously. Inhibition of human aromatase, steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) activities was investigated with in vitro radiosubstrate incubations. Some of the test compounds were found to be potent inhibitors of the STS. A compound bearing ferrocenyl side chain on the C-2 displayed a reversible inhibition, whereas C-16 and C-17 derivatives displayed competitive irreversible binding mechanism toward the enzyme. 17α-Triazolyl-ferrocene derivatives of 17β-estradiol exerted outstanding inhibitory effect and experiments demonstrated a key role of the ferrocenyl moiety in the enhanced binding affinity. Submicromolar IC50 and Ki parameters enroll these compounds to the group of the most effective STS inhibitors published so far. STS inhibitory potential of the steroidal ferrocenes may lead to the development of novel compounds able to suppress in situ biosynthesis of 17β-estradiol in target tissues.

scholarly journals Mechanisms Underlying Adaptation of Respiratory Network Activity to Modulatory Stimuli in the Mouse Embryo

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Marc Chevalier ◽  
Rafaël De Sa ◽  
Laura Cardoit ◽  
Muriel Thoby-Brisson
Keyword(s):  
Ph Regulation ◽  
Respiratory Rhythm ◽  
Network Activity ◽  
Pacemaker Neurons ◽  
Functional Flexibility ◽  
Respiratory Rhythmogenesis ◽  
Brainstem Slice ◽  
Respiratory Network ◽  
The Impact

Breathing is a rhythmic behavior that requires organized contractions of respiratory effector muscles. This behavior must adapt to constantly changing conditions in order to ensure homeostasis, proper body oxygenation, and CO2/pH regulation. Respiratory rhythmogenesis is controlled by neural networks located in the brainstem. One area considered to be essential for generating the inspiratory phase of the respiratory rhythm is the preBötzinger complex (preBötC). Rhythmogenesis emerges from this network through the interplay between the activation of intrinsic cellular properties (pacemaker properties) and intercellular synaptic connections. Respiratory activity continuously changes under the impact of numerous modulatory substances depending on organismal needs and environmental conditions. The preBötC network has been shown to become active during the last third of gestation. But only little is known regarding the modulation of inspiratory rhythmicity at embryonic stages and even less on a possible role of pacemaker neurons in this functional flexibility during the prenatal period. By combining electrophysiology and calcium imaging performed on embryonic brainstem slice preparations, we provide evidence showing that embryonic inspiratory pacemaker neurons are already intrinsically sensitive to neuromodulation and external conditions (i.e., temperature) affecting respiratory network activity, suggesting a potential role of pacemaker neurons in mediating rhythm adaptation to modulatory stimuli in the embryo.

Spatiotemporal Activity Patterns During Respiratory Rhythmogenesis in the Rat Ventrolateral Medulla

2006 ◽  
Vol 95 (3) ◽  
pp. 1982-1991 ◽  
Author(s):  
Jonathan A. N. Fisher ◽  
Vitaliy A. Marchenko ◽  
Arjun G. Yodh ◽  
Robert F. Rogers
Keyword(s):  
Optical Imaging ◽  
High Speed ◽  
Spatial Organization ◽  
Imaging Techniques ◽  
Respiratory Rhythm ◽  
Respiratory Neurons ◽  
Ventrolateral Medulla ◽  
Respiratory Rhythmogenesis ◽  
In Situ Preparation

One of the most important brain rhythms is that which generates involuntary breathing movements. The lower brain stem contains neural circuitry for respiratory rhythm generation in mammals. To date, microsectioning and selective lesioning studies have revealed anatomical regions necessary for respiratory rhythmogenesis. Although respiratory neurons distributed within these regions can be identified by their firing patterns in different phases of the respiratory cycle, conventional electrophysiology techniques have limited the study of spatial organization within this network. Optical imaging techniques offer the potential for monitoring the spatiotemporal activity of large groups of neurons simultaneously. Using high-speed voltage-sensitive dye imaging and spatial correlation analysis in an arterially perfused in situ preparation of the juvenile rat, we determined the spatial distribution of respiratory neuronal activity in a region of the ventrolateral respiratory group containing the pre-Bötzinger complex (pBC) during spontaneous eupneic breathing. While distinctly pre- and postinspiratory-related responses were spatially localizable on length scales less than 100 μm, we found the studied area on whole exhibited a spatial mixture of phase-spanning and postinspiratory-related activity. Additionally, optical recordings revealed significant widespread hyperpolarization, suggesting inhibition in the same region during expiration. This finding is consistent with the hypothesis that inhibitory neurons play a crucial role in the inspiration-expiration phase transition in the pBC. To our knowledge this is the first optical imaging of a near fully intact in situ preparation that exhibits both eupneic respiratory activity and functional reflexes.

scholarly journals Mylohyoid discharge of the in situ rat: a probe of pontile respiratory activities in eupnea and gasping

2010 ◽  
Vol 108 (3) ◽  
pp. 614-620 ◽  
Author(s):  
Walter M. St.-John ◽  
Alison H. Rudkin ◽  
J. C. Leiter
Keyword(s):  
Respiratory Rhythm ◽  
Motor Nucleus ◽  
Trigeminal Motor Nucleus ◽  
In Situ Preparation ◽  
Mylohyoid Nerve ◽  
Respiratory Modulation ◽  
Additional Support ◽  
Respiratory Rhythms

Our purpose was to characterize respiratory-modulated activity of the mylohyoid nerve. Since its motoneurons are in the trigeminal motor nucleus, mylohyoid discharge could serve as a probe of the role of pontile mechanisms in the generation of respiratory rhythms. Studies were performed in the decerebrate, perfused in situ preparation of the rat. Phrenic discharge was recorded as the index of the respiratory rhythm. In eupnea, the mylohyoid nerve discharged primarily during neural expiration, in the period between phrenic bursts. This expiratory discharge increased greatly in hypoxia and fell in hypercapnia. The hypoxia-induced increase in mylohyoid discharge was due, at least in part, to a direct influence of hypoxia on the brain stem. In ischemia, phrenic discharge increased, and then declined to apnea, which was succeeded by gasping. The mylohyoid nerve discharged tonically during the apneic period, but still declined during each of the phrenic bursts of gasping. This maintenance of a respiratory-modulation of the mylohyoid discharge in gasping supports the concept that a release of medullary mechanisms, rather than a ubiquitous suppression of pontile influences, underlies the neurogenesis of gasping. Results also provide additional support for our conclusion that activity of any single cranial nerve does not provide an accurate index of the type of respiratory rhythm, be it eupnea or gasping.

Glutamatergic Antagonism in the NTS Decreases Post-Inspiratory Drive and Changes Phrenic and Sympathetic Coupling During Chemoreflex Activation

2010 ◽  
Vol 103 (4) ◽  
pp. 2095-2106 ◽  
Author(s):  
João H. Costa-Silva ◽  
Daniel B. Zoccal ◽  
Benedito H. Machado
Keyword(s):  
Nucleus Tractus Solitarius ◽  
Respiratory Rhythm ◽  
Glutamatergic Neurotransmission ◽  
Peripheral Chemoreceptor ◽  
Respiratory Parameters ◽  
Before And After ◽  
Peripheral Chemoreflex ◽  
Working Heart

For a better understanding of the processing at the nucleus tractus solitarius (NTS) level of the autonomic and respiratory responses to peripheral chemoreceptor activation, herein we evaluated the role of glutamatergic neurotransmission in the intermediate (iNTS) and caudal NTS (cNTS) on baseline respiratory parameters and on chemoreflex-evoked responses using the in situ working heart-brain stem preparation (WHBP). The activities of phrenic (PND), cervical vagus (cVNA), and thoracic sympathetic (tSNA) nerves were recorded before and after bilateral microinjections of kynurenic acid (Kyn, 5 nmol/20 nl) into iNTS, cNTS, or both simultaneously. In WHBP, baseline sympathetic discharge markedly correlated with phrenic bursts (inspiration). However, most of sympathoexcitation elicited by chemoreflex activation occurred during expiration. Kyn microinjected into iNTS or into cNTS decreased the postinspiratory component of cVNA and increased the duration and frequency of PND. Kyn into iNTS produced no changes in sympathoexcitatory and tachypneic responses to peripheral chemoreflex activation, whereas into cNTS, a reduction of the sympathoexcitation, but not of the tachypnea, was observed. The pattern of phrenic and sympathetic coupling during the chemoreflex activation was an inspiratory-related rather than an expiratory-related sympathoexcitation. Kyn simultaneously into iNTS and cNTS produced a greater decrease in postinspiratory component of cVNA and increase in frequency and duration of PND and abolished the respiratory and autonomic responses to chemoreflex activation. The data show that glutamatergic neurotransmission in the iNTS and cNTS plays a tonic role on the baseline respiratory rhythm, contributes to the postinspiratory activity, and is essential to expiratory-related sympathoexcitation observed during chemoreflex activation.

Effect of Dipyridamole on Spontaneous Platelet Aggregation in Whole Blood Decreases with the Time After Venepuncture: Evidence for the Role of ADP

1987 ◽  
Vol 58 (02) ◽  
pp. 744-748 ◽  
Author(s):  
A R Saniabadi ◽  
G D O Lowe ◽  
J C Barbenel ◽  
C D Forbes
Keyword(s):  
Platelet Aggregation ◽  
Correlation Coefficient ◽  
Whole Blood ◽  
Blood Platelet ◽  
Inhibitory Effect ◽  
Time Interval ◽  
Adp Receptor ◽  
Spontaneous Platelet Aggregation

SummarySpontaneous platelet aggregation (SPA) was studied in human whole blood at 3, 5, 10, 20, 30, 40 and 60 minutes after venepuncture. Using a whole blood platelet counter, SPA was quantified by measuring the fall in single platelet count upon rollermixing aliquots of citrated blood at 37° C. The extent of SPA increased with the time after venepuncture, with a correlation coefficient of 0.819. The inhibitory effect of dipyridamole (Dipy) on SPA was studied: (a) 10 μM at each time interval; (b) 0.5-100 μM at 3 and 30 minutes and (c) 15 μM in combination with 100 μM adenosine, 8 μM 2-chloroadenosine (2ClAd, an ADP receptor blocker) and 50 μM aspirin. There was a rapid decrease in the inhibitory effect of Dipy with the time after venepuncture; the correlation coefficient was -0.533. At all the concentrations studied, Dipy was more effective at 3 minutes than at 30 minutes after venepuncture. A combination of Dipy with adenosine, 2ClAd or aspirin was a more effective inhibitor of SPA than either drug alone. However, when 15 μM Dipy and 10 μM Ad were added together, the inhibitory effect of Dipy was not increased significantly, suggesting that Dipy inhibits platelet aggregation independent of Ad. The increase in SPA with the time after venepuncture was abolished when blood was taken directly into the anticoagulant containing 5 μM 2ClAd. It is suggested that ADP released from the red blood cells is responsible for the increased platelet aggregability with the time after venepuncture and makes a serious contribution to the artifacts of in vitro platelet function studies.

Inhibition of the Activities of α2-Plasmin inhibitor (PI) and CI inhibitor (CI-Inh) by the Synthetic Fibrinolytic Agent, 3-Hydroxypropyl Flufenamide (Flu-HPA)

1979 ◽  
Author(s):  
L Miles ◽  
J Burnier ◽  
M Verlander ◽  
M Goodman ◽  
A Kleiss ◽  
...  
Keyword(s):  
Plasminogen Activators ◽  
Inhibitory Effect ◽  
Mechanisms Of Action ◽  
Flufenamic Acid ◽  
Clot Lysis ◽  
Factor Xiia ◽  
Dependent Inhibition ◽  
Normal Human ◽  
Plasmin Inhibitor

Flu-HPA is one of a series of flufenamic acid derivations that enhances plasminogen-dependent clot lysis in vitro. Studies of possible mechanisms of action of Flu-HPA were undertaken. The influence of Flu-HPA on the inhibition of purified plasmin by purified PI was studied. PI activity was assessed by its inhibition of the clevage of the tripeptide S-2251 (H-D-Val-Leu-Lys-pNA) by plasmin. Flu-HPA was dissolved in DMF or in methonol and preincubated with PI before addition of plasmin. At Flu-HPA concentrations greater than 1mM and up to 60mM, the inhibitory activity of PI was totally lost. The inhibitory effect of normal human plasma on plasmin was also completely abolished at concentrations of Flu-HPA between 2.5 and 40mM. The effect of Flu-HPA on the inhibition of purified plasma kallikrein by purified CI-Inh was also studied. CI-Inh activity was measured by its inhibition of cleavage of the tripeptide Bz-Pro-Phe-Arg-pNA by kallikrein. When Flu-HPA, dissolved in DMF or in methonol, was preincubated with CI-Inh, a concentration dependent inhibition of CI-Inh activity was observed. CI-Inh activity was abolished by concentrations of Flu-HPA greater than 1mM. Flu-HPA also inhibited the activity of CI-Inh on purified Factor XIIa. These observations suggest that this flufenamic acid derivative may enhance fibrinolysis not only by inhibiting PI activity but also by decreasing the inactivation of plasminogen activators by CI-Inh.

Sign in / Sign up

Export Citation Format

Share Document