For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
16
views
47
references
 Top references
cited by
3
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      223
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The noncarbonic anhydrase inhibiting acetazolamide analog N-methylacetazolamide reduces the hypercapnic, but not hypoxic, ventilatory response

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Previous studies have shown that the carbonic anhydrase (CA) inhibitors acetazolamide (AZ) and methazolamide (MZ) have inhibiting actions on breathing. Classically these have been attributed to CA inhibition, but other effects unrelated to CA inhibition have been identified in other tissues. To explore this possibility in the control of ventilation by the central nervous system, we investigated whether an AZ-analog without CA inhibiting properties, by virtue of a single methylation on the sulfonamide moiety, N-methylacetazolamide (NMA), would still display similar actions to acetazolamide and methazolamide. NMA (20 mg kg −1) was given intravenously to anesthetized cats and we measured the responses to steady-state isocapnic hypoxia and stepwise changes in end-tidal pco 2 before and after infusion of this AZ analog using the technique of end-tidal forcing. NMA caused a large decrease in the apneic threshold and CO 2 sensitivity very similar to those previously observed with AZ and MZ, suggesting that these effects are mediated independently of CA inhibition. In contrast to acetazolamide, but similar to methazolamide, NMA did not affect the steady-state isocapnic hypoxic response. In conclusion, our data reveal complex effects of sulfonamides with very similar structure to AZ that reveal both CA-dependent and CA-independent effects, which need to be considered when using AZ as a probe for the role of CA in the control of ventilation.

          Related collections

          Most cited references47

          • Record: found
          • Abstract: found
          • Article: not found

          The ventilatory response to hypoxia in mammals: mechanisms, measurement, and analysis.

          Albert Dahan, Luc Teppema (2010)
          The respiratory response to hypoxia in mammals develops from an inhibition of breathing movements in utero into a sustained increase in ventilation in the adult. This ventilatory response to hypoxia (HVR) in mammals is the subject of this review. The period immediately after birth contains a critical time window in which environmental factors can cause long-term changes in the structural and functional properties of the respiratory system, resulting in an altered HVR phenotype. Both neonatal chronic and chronic intermittent hypoxia, but also chronic hyperoxia, can induce such plastic changes, the nature of which depends on the time pattern and duration of the exposure (acute or chronic, episodic or not, etc.). At adult age, exposure to chronic hypoxic paradigms induces adjustments in the HVR that seem reversible when the respiratory system is fully matured. These changes are orchestrated by transcription factors of which hypoxia-inducible factor 1 has been identified as the master regulator. We discuss the mechanisms underlying the HVR and its adaptations to chronic changes in ambient oxygen concentration, with emphasis on the carotid bodies that contain oxygen sensors and initiate the response, and on the contribution of central neurotransmitters and brain stem regions. We also briefly summarize the techniques used in small animals and in humans to measure the HVR and discuss the specific difficulties encountered in its measurement and analysis.
          Article 0 comments Cited 104 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Acetazolamide improves loop gain but not the other physiological traits causing obstructive sleep apnoea.

            Bradley A Edwards, Scott Sands, Danny J Eckert … (2012)
            There is some evidence to suggest that acetazolamide may improve obstructive sleep apnoea (OSA).However, how acetazolamide affects the key traits causing OSA remains uncertain. We aimed to investigate the effect of acetazolamide on the traits contributing to OSA and its severity. Acetazolamide (500 mg twice daily) was administered for 1 week to 13 OSA subjects. Pharyngeal anatomy/collapsibility, loop gain (LG), upper-airway muscle responsiveness (gain) and the arousal threshold were determined using multiple 3 min 'CPAP pressure drops': pharyngeal anatomy/collapsibility was quantified as the ventilation at CPAP=0. LG was defined as the ratio of the ventilatory overshoot to the preceding reduction in ventilation. Upper-airway gain was taken as the ratio of the increase in ventilation to the increase in ventilatory drive across the drop. Arousal threshold was quantified as the level of ventilatory drive associated with arousal. The apnoea-hypopnoea index (AHI)was assessed on separate nights using standard polysomnography. Acetazolamide reduced the median [interquartile range] LG (3.4 [2.4-5.4] versus 2.0 [1.4-3.5]; P <0.05) and NREM AHI (50 [36-57] versus 24 [13-42] events h-1; P <0.05), but did not significantly alter pharyngeal anatomy/collapsibility, upper-airway gain, or arousal threshold. There was a modest correlation between the percentage reduction in LG and the percentage reduction in AHI (r =0.660, P =0.05). Our findings suggest that acetazolamide can improve OSA, probably due to reductions in the sensitivity of the ventilatory control system. Identification of patients who may benefit from reductions in LG alone or in combination with other therapies to alter the remaining traits may facilitate pharmacological resolution of OSA in the future.
            Article 0 comments Cited 67 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study.

              S Javaheri (2006)
              Acetazolamide is a mild diuretic and a respiratory stimulant. It is used to treat periodic breathing at high altitude. To determine the therapeutic efficacy of acetazolamide on central sleep apnea associated with heart failure. Twelve male patients with stable systolic heart failure whose initial polysomnograms showed more than 15 episodes per hour of apnea and hypopnea participated in the study. The patients were randomized to a double-blind cross-over protocol with acetazolamide or placebo, taken 1 h before bedtime for six nights with 2 wk of washout. Polysomnography, pulmonary function tests, arterial blood gases, and left ventricular ejection fraction were obtained initially along with a sleep questionnaire, history, and physical examination. Baseline measurements were repeated at the end of each arm. There were no significant differences between parameters at baseline and placebo. In comparing placebo with acetazolamide, the hourly number of episodes of central apnea (49 +/- 28 vs. 23 +/- 21 [mean +/- SD]; p = 0.004) and the percentage of total sleep time spent below an arterial oxyhemoglobin saturation of 90% (19 +/- 32 vs. 6 +/- 13%; p = 0.01) decreased significantly. Acetazolamide improved subjective perception of overall sleep quality (p = 0.003), feeling rested on awakening (p = 0.007), daytime fatigue (p = 0.02), and falling asleep unintentionally during daytime (p = 0.002). In patients with heart failure, administration of a single dose of acetazolamide before sleep improves central sleep apnea and related daytime symptoms.
              Article 0 comments Cited 51 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Physiol Rep
                Journal ID (iso-abbrev): Physiol Rep
                Journal ID (publisher-id): phy2
                Title: Physiological Reports
                Publisher: John Wiley & Sons, Ltd (Chichester, UK )
                ISSN (Print): 2051-817X
                ISSN (Electronic): 2051-817X
                Publication date Collection: August 2015
                Publication date (Electronic): 19 August 2015
                Volume: 3
                Issue: 8
                Electronic Location Identifier: e12484
                Affiliations
                [1 ]Department of Anesthesiology, Leiden University Medical Centre Leiden, The Netherlands
                [2 ]Pulmonary and Critical Care Medicine, VA Puget Sound Health Care System, University of Washington Seattle, Washington, USA
                Author notes
                Correspondence Luc J. Teppema, Department of Anesthesiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands., Tel: +31 71 5263607, Fax: +31 71 5266782, e-mail: l.j.s.m.teppema@ 123456lumc.nl

                Funding Information No funding information provided.

                Article
                DOI: 10.14814/phy2.12484
                PMC ID: 4562570
                PubMed ID: 26290531
                SO-VID: 0dddfcea-43c5-451d-8b82-e51c5caf2753
                Copyright © © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
                License:

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 06 July 2015
                Date accepted : 09 July 2015
                Categories
                Subject: Original Research

                Keywords: carbon dioxide,carbonic anhydrase,hypoxia,n-methyl acetazolamide,ventilation
                Data availability:
                Keywords: carbon dioxide, carbonic anhydrase, hypoxia, n-methyl acetazolamide, ventilation

                Comments

                Comment on this article

                scite_

                Similar content223

                See all similar

                Cited by3

                See all cited by

                Most referenced authors260

                See all reference authors