The Journal of physiology
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The Journal of physiology · Mar 2012
Acid-sensing ion channel subtype 3 function and immunolabelling increases in skeletal muscle sensory neurons following femoral artery occlusion.
Sympathetic nerve activity and arterial blood pressure responses to static hindlimb muscle contractions are greater in rats with femoral arteries that were previously ligated (24-72 h earlier) than in control rats. Studies further demonstrate that acid-sensing ion channel subtype 3 (ASIC(3)) in thin-fibre muscle afferents contributes to the amplified reflex muscle responses observed in occluded rats, probably due to enhanced ASIC(3) expression in muscle sensory neurons. The purpose of this study was to characterize acid-induced current with activation of ASIC(3) in dorsal root ganglion (DRG) neurons of control rats and rats with 24 h of femoral occlusion using whole-cell patch clamp methods. ⋯ Moreover, the percentage of DRG neurons with ASIC(3)-like currents is greater after arterial occlusion compared with control. Furthermore, results from double immunofluorescence experiments show that femoral artery occlusion mainly augments ASIC(3) expression within DRG neurons projecting C-fibre afferents. Taken together, these data suggest that (1) the majority of current responses to pH 6.7 are ASIC(3)-like in DRG neurons with nerve endings in the hindlimb muscles, (2) a greater acid-induced current responding to pH 6.7 develops when hindlimb arterial blood supply is deficient under ischaemic conditions, and (3) increased ASIC(3) expression is largely observed in thin C-fibres of DRG neurons after hindlimb ischaemia.
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The Journal of physiology · Mar 2012
Randomized Controlled Trial Clinical TrialAcetazolamide improves loop gain but not the other physiological traits causing obstructive sleep apnoea.
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. ⋯ 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.
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The Journal of physiology · Mar 2012
Randomized Controlled Trial Clinical TrialEffects of acetazolamide on cerebrovascular function and breathing stability at 5050 m.
One of the many actions of the carbonic anhydrase inhibitor, acetazolamide (ACZ), is to accelerate acclimatisation and reduce periodic breathing during sleep. The mechanism(s) by which ACZ may improve breathing stability, especially at high altitude, remain unclear. We tested the hypothesis that acute I. ⋯ V. ACZ elevates cerebrovascular reactivity and improves breathing stability at altitude, independent of changes in peripheral or central chemoreflex sensitivities. We speculate that Pa,CO₂-mediated elevations in cerebral perfusion and an enhanced cerebrovascular reactivity may partly account for the improved breathing stability following ACZ at high altitude.