Effects of inhibiting carbonic anhydrase on isometric contraction of frog skeletal muscle.

Scheid, P.; Siffert, Winfried

doi:10.1113/jphysiol.1985.sp015634

Cited by 22 publications

(7 citation statements)

References 22 publications

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“…In a frog gastrocnemius/ischiadic nerve preparation, Scheid and Siffert (30) showed that inhibition of local carbonic anhydrase reduced the isometric force on indirect (but not direct) stimulation. Ultrastructural studies of rat soleus muscle (12) provided no clue as to a specific location of CA on the sarcolemma, for example, associated with motor end-plates.…”

Section: Discussionmentioning

confidence: 98%

Low-dose Acetazolamide Does Affect Respiratory Muscle Function in Spontaneously Breathing Anesthetized Rabbits

Kiwull-Schöne

Teppema

Kiwull

2001

Am J Respir Crit Care Med

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Patients with chronic obstructive pulmonary diseases (COPD) and/or central sleep apnea are sometimes treated with the carbonic anhydrase inhibitor acteazolamide to improve blood gas values. Studies have shown that this agent may have a complicated effect on lung ventilation, because carbonic anhydrase has a widespread distribution within the body, particularly in tissues involved in the control of breathing. To investigate whether acetazolamide may have (neuro)muscular effects on respiration, we measured the responses of ventilation, phrenic nerve activity, and transpulmonary pressure to changes in arterial PCO2 before and after intravenous administration of a low-dose (4.6 +/- 0.2 mg x kg(-1), mean +/- SEM) of this inhibitor in anesthetized spontaneously breathing rabbits. The agent decreased the mean resting end-tidal PCO2 by 1 kPa and increased ventilation from 258 +/- 15 to 292 +/- 14 ml x min(-1) x kg(-1) (p < or = 0.05). The ventilatory and tidal volume responses to CO2 were reduced, and the response curves were shifted to lower PCO2 values. At the level of phrenic activity, however, the response was shifted leftward without altering CO2 sensitivity. With an unchanged lung compliance, the slopes of the relationships between tidal volume and phrenic activity and that between the tidal change in transpulmonary pressure and phrenic amplitude were both reduced by about 40%, indicating an action of acetazolamide on (neuro)muscular level. The results raise the suggestion that treatment of some hypercapnic COPD patients with acetazolamide may have undesired clinical implications, particularly in those with already weakened respiratory muscles.

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Section: Discussionmentioning

confidence: 98%

Low-dose Acetazolamide Does Affect Respiratory Muscle Function in Spontaneously Breathing Anesthetized Rabbits

Kiwull-Schöne

Teppema

Kiwull

2001

Am J Respir Crit Care Med

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“…It has been reported that in frog muscle carbonic anhydrase plays a role in neuromuscular transmission (Scheid & Siffert, 1985 Barclay (1987) found that the isometric tetanic force is decreased in the presence of cyanate only when PC02 is increased. With acetazolamide no effect on isometric force could be observed.…”

Section: Discussionmentioning

confidence: 99%

“…Sarcolemmal CA is catalytically active in the extracellular space and has been suggested to accelerate the uptake by the blood of the CO2 produced in the muscle (Geers, Gros & Girtner, 1985). (ii) CA inhibition has been reported to impair neuromuscular transmission (Scheid & Siffert, 1985). (iii) Barclay (1987) reported that isolated soleus muscles of the mouse incubated with CA inhibitor cyanate, but not with acetazolamide, show a decrease in tetanic tension development.…”

Section: Introductionmentioning

confidence: 99%

Effects of carbonic anhydrase inhibitors on contraction, intracellular pH and energy‐rich phosphates of rat skeletal muscle.

Geers

Gros

1990

The Journal of Physiology

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SUMMARY1. The effects of carbonic anhydrase inhibitors on contractile parameters, intracellular pH (pHi) and energy-rich phosphates were studied in isolated rat soleus and extensor digitorum longs (EDL) muscles.2. The muscles were incubated either in Ringer solutions (95% 02/5% CO2 = control) or in solutions to which one of the inhibitors, 5 x 10' M-chlorzolamide or 10-2 m-NaCNO, had been added. Muscles were stimulated directly and contracted under isometric conditions.3. Compared with control muscles, both inhibitor-treated muscles showed a significantly decreased tetanic force and an increased half-relaxation time of twitches and tetani. Chlorzolamide increased time-to-peak in both muscles. Cyanate decreased isometric twitch force in both muscles.4. Both inhibitors decreased pHi in both muscles; chlorzolamide by 0.1 unit, cyanate by 0-4 unit in soleus and by 0-8 unit in EDL.5. Chlorzolamide increased the concentrations of creatine and inorganic phosphate (Pi) in soleus (the effect of chlorzolamide was not studied in EDL). Cyanate caused these same changes in soleus as well as EDL and in addition decreased the concentrations of ATP and phosphocreatine in soleus and EDL.6. In muscles acidified by either low external HCO3-(2 mM) or by elevated Pco2(30 % CO2 in the gas phase) in the bath, decreases in isometric force and increases in half-relaxation time of tetani were observed. In addition there were increases in muscle Pi. These effects were more pronounced with 30% CO2 than with 2 mM-HCO3-. 7. Neither acidifying solutions prolonged either half-relaxation time or time-topeak of twitches.8. We conclude that carbonic anhydrase inhibition exerts its effect (a) on isometric tension at least partly via an elevated Pi (perhaps in combination with lowered pHi);(b) on the half-relaxation time of tetani by means of lowered pHi and elevated concentration of Pi; (c) on relaxation and time-to-peak of twitches by some unknown mechanism, neither directly by a change in pHi nor in Pi.MS 7639

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“…When larger doses are infused during hypoxia, an initial period of apnoea ensues (Teppema et al 1992 (Geers & Gros, 1991). Scheid & Siffert (1985) showed that concentrations > 104 0 i acetazolamide wN-ere necessary to inhibit maximal isometric force of frog skeletal muscle by 50%. Barclay (1987) Sw\enson & Hughes, 1993) or no change in slope, but only an upward shift of the response curve (cf.…”

Section: I Wagenaar Anid Othersmentioning

confidence: 99%

The effect of low‐dose acetazolamide on the ventilatory CO2 response curve in the anaesthetized cat.

Wagenaar

Teppema

Berkenbosch

et al. 1996

The Journal of Physiology

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1. The effect of 4 mg kg-' acetazolamide (i.v.) on the slope (S) and intercept on the Pa,co2 axis (B) of the ventilatory CO2 response curve of anaesthetized cats with intact or denervated carotid bodies was studied using the technique of dynamic end-tidal forcing.2. This dose did not induce an arterial-to-end-tidal PCO2 (P(a-ET),co2) gradient, indicating that erythrocytic carbonic anhydrase was not completely inhibited. Within the first 2 h after administration, this small dose caused only a slight decrease in mean standard bicarbonate of 1P8 and 1P7 mmol F' in intact (n = 7) and denervated animals (n = 7), respectively. Doses of acetazolamide larger than 4 mg kg-1 (up to 32 mg kg-1) caused a significant increase in the P(a-ET),CO2 gradient. from 4'0 + 05 to 3'0 + 0-6 kPa, respectively, not significantly different from the changes encountered in the denervated animals. 5. It is argued that the effect of acetazolamide on the CO2 sensitivity of the peripheral chemoreflex loop in intact cats may be caused by a direct effect on the carotid bodies. Both in intact and in denervated animals the effects of the drug on S, and B may not be due to a direct action on the central nervous system, but rather to an effect on cerebral vessels resulting in an altered relationship between brain blood flow and brain tissue PCo2

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Effects of inhibiting carbonic anhydrase on isometric contraction of frog skeletal muscle.

Cited by 22 publications

References 22 publications

Low-dose Acetazolamide Does Affect Respiratory Muscle Function in Spontaneously Breathing Anesthetized Rabbits

Low-dose Acetazolamide Does Affect Respiratory Muscle Function in Spontaneously Breathing Anesthetized Rabbits

Effects of carbonic anhydrase inhibitors on contraction, intracellular pH and energy‐rich phosphates of rat skeletal muscle.

The effect of low‐dose acetazolamide on the ventilatory CO2 response curve in the anaesthetized cat.

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