Magnesium sulfate (MgSO4) may be useful in patients failing conventional therapy for asthma. Studies suggest that Mg2+ is a voltage-dependent Ca2+ channel (VDC) antagonist, causing greater relaxation in airways contracted with KCl than with cholinergic agonists. This is consistent with the fact that in KCl-induced tension, both initiation and maintenance of contraction require Ca2+ entry through VDCs, but in cholinergic-induced tension, initiation of contraction is mediated by receptor-operated Ca2+ channels, and only maintenance requires VDCs. However, there is little evidence showing involvement of VDCs in airway contraction to physiologic agonists, such as leukotriene D4 (LTD4), an inflammatory mediator in asthma. The mechanism of LTD4-mediated airway contraction is not precisely known. Thus, this study was designed to evaluate the effect of MgSO4 on LTD4-induced airway tone. Methods. Newborn guinea pig tracheal ring segments (n=7-9) were constricted to 2 grams tension with acetylcholine (ACh), KCl, or LTD4. Changes in isometric tension to cumulative additions of MgSO4 (1.2-11.2 mM) were measured. Results. After constriction with ACh, MgSO4 produced dose-dependent airway relaxation, at maximum by 33±6%. After constriction with LTD4, MgSO4 relaxed airway tone by 42±8%, similar to that produced after constriction with ACh (p=NS). However, after constriction with KCl, MgSO4 produced greater relaxation (74±7%, p<0.0001). Conclusions. MgSO4 significantly relaxes leukotriene-induced airway contraction in vitro, supporting its use clinically in reducing inflammatory-mediated airway hyperresponsiveness. The similarity of relaxation responses after constriction with ACh and LTD4 suggests that, as with ACh, maintenance of contraction to LTD4 may require VDCs.

Funded by: US Army HSC and Research Board of Kapiolani Medical Center.