The hypoxia-induced facilitation of augmented breaths is suppressed by the common effect of carbonic anhydrase inhibition

被引:19
作者
Bell, Harold J. [1 ,2 ]
Haouzi, Philippe [1 ,2 ]
机构
[1] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Med, Hershey, PA 17033 USA
[2] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA
关键词
Hypocapnia; Sighs; Breathing stability; CHEYNE-STOKES RESPIRATION; LOW-DOSE ACETAZOLAMIDE; VENTILATORY RESPONSE; HIGH-ALTITUDE; BRAIN-STEM; BLOOD-FLOW; MULTIFUNCTIONAL NETWORK; SYNAPTIC MECHANISMS; BAROMETRIC METHOD; NEURAL-NETWORK;
D O I
10.1016/j.resp.2010.04.002
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The typical respiratory response to hypoxia includes a dramatic facilitation of augmented breaths (ABs) or 'sighs' in the breathing rhythm. We recently found that when acetazolamide treatment is used to promote CO2 retention and counteract alkalosis during exposure to hypoxia, then the hypoxia-induced facilitation of ABs is effectively prevented. These results indicate that hyperventilation-induced hypocapnia/alkalosis is an essential factor involved in the hypoxia-induced facilitation of augmented breaths. However, acetazolamide is also known to decrease the sensitivity of the arterial chemoreceptors. Therefore, the question remains as to whether acetazolamide prevents the facilitation of ABs during hypoxia by offsetting the effects of respiratory alkalosis, or alternatively by suppressing carotid body afferent activity. In the present study, we addressed this question by studying the effects of treatment with an alternative carbonic anhydrase inhibitor, methazolamide, which has been reported to leave carotid body responsiveness to hypoxia intact. Respiratory variables were monitored before, during and after 2 days of methazolamide treatment (10 mg kg(-1) IP, bid) in unsedated and unrestrained adult male rats. Pretreatment, the number of ABs observed in a 5 min observation window was 1.2 +/- 0.8 and 17.4 +/- 3.8 in room air and hypoxia, respectively. During methazolamide treatment, the facilitation of ABs in hypoxia was rapidly and reversibly suppressed such that ABs we no longer significantly more frequent than they were in room air. The present results demonstrate that the hypoxia-induced facilitation of ABs can be suppressed via the general effects of carbonic anhydrase inhibition, which are common to both acetazolamide and methazolamide. We discuss these results as they pertain to the mechanisms regulating augmented breath production, and the possible association between hypocapnia/alkalosis and sleep disordered breathing. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:201 / 211
页数:11
相关论文
共 79 条
[1]   ORIGIN AND REGULATION OF SPONTANEOUS DEEP BREATHS [J].
BARTLETT, D .
RESPIRATION PHYSIOLOGY, 1971, 12 (02) :230-+
[2]  
BELL NJ, 2009, AM J PHYSIOL-REG I, V297, pR370
[3]  
BELL NJ, 2009, AM J PHYSIOL-REG I, V296, pR334
[4]   PATTERN OF VENTILATION IN YOUNG ADULTS [J].
BENDIXEN, HH ;
SMITH, GM ;
MEAD, J .
JOURNAL OF APPLIED PHYSIOLOGY, 1964, 19 (02) :195-&
[5]   INTERACTION OF PERIPHERAL AND CENTRAL RESPIRATORY DRIVES IN CATS .1. EFFECTS OF SODIUM CYANIDE AS A PERIPHERAL CHEMORECEPTOR STIMULUS AT DIFFERENT LEVELS OF CSF-PH [J].
BERGER, W ;
BERGER, K ;
BERNDT, J ;
GIESE, K .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1978, 374 (03) :205-210
[6]   MECHANISMS OF HYPOXIA-INDUCED PERIODIC BREATHING DURING SLEEP IN HUMANS [J].
BERSSENBRUGGE, A ;
DEMPSEY, J ;
IBER, C ;
SKATRUD, J ;
WILSON, P .
JOURNAL OF PHYSIOLOGY-LONDON, 1983, 343 (OCT) :507-524
[7]   EFFECTS OF ACETAZOLAMIDE ON CEREBRAL ACID-BASE-BALANCE [J].
BICKLER, PE ;
LITT, L ;
BANVILLE, DL ;
SEVERINGHAUS, JW .
JOURNAL OF APPLIED PHYSIOLOGY, 1988, 65 (01) :422-427
[8]   Gray matter blood flow change is unevenly distributed during moderate isocapnic hypoxia in humans [J].
Binks, Andrew P. ;
Cunningham, Vincent J. ;
Adams, Lewis ;
Banzett, Robert B. .
JOURNAL OF APPLIED PHYSIOLOGY, 2008, 104 (01) :212-217
[9]  
Brown, 2000, Paediatr Anaesth, V10, P696, DOI 10.1111/j.1460-9592.2000.ab01p.x
[10]   CHARACTERISTICS AND RATE OF OCCURRENCE OF SPONTANEOUS AND PROVOKED AUGMENTED BREATHS [J].
CHERNIACK, NS ;
VONEULER, C ;
GLOGOWSKA, M ;
HOMMA, I .
ACTA PHYSIOLOGICA SCANDINAVICA, 1981, 111 (03) :349-360