Hard metal-induced disease:: Effects of metal cations in vitro on guinea pig isolated airways

Inhalation of dust from hard metal (HM), a mixture of tungsten carbide, cobalt, and other metals, can cause interstitial alveolitis, fibrosis, and asthma in the workplace. Some effects of HM could occur after the metals dissolve in the lung. We examined whether chloride salts of metals in HM alloys can elicit responses or modify reactivity to methacholine (MCh) or responses to electric field stimulation (EFS) in guinea pig tracheal strips. In unstimulated strips, Co2+, Cd2+, and Ni2+ evoked contractions (>3 X 10(-6) M), while Ta5+, Zn2+, Cr2+, and Cr3+ caused weak relaxations (> 10(-5) M). In strips contracted with MCh (3 X 10(-7) M), Co2+ and Ni2+ also caused relaxation in lower concentrations while the other metals caused weak relaxation only in high concentrations (> 10(-4) M). The metals were generally without effect on reactivity to MCh, except that Cd2+ inhibited and Ni2+ potentiated some responses. The effects of selected metals (10(-6) M; Cr3+, Ni2+, Cd2+, and Co2+) on EFS-induced contractile and relaxant responses were examined (+/-L-MCh; +/- 10(-6) M indomethacin (Indo), 30 min). No metal had any effect on the excitatory nonadrenergic, noncholinergic-mediated contraction phase. Cd2+ and Ni2+ inhibited cholinergically mediated contractions of unstimulated strips (+Indo), whereas Cr2+ both inhibited (-MCh, -Indo) and potentiated (-Indo,+MCh; +Indo, +MCh) contractile responses. Cr3+ was the only metal to inhibit the inhibitory nonadrenergic, noncholinergic-mediated relaxation phase (+/- MCh; -Indo). Co2+ had no effect at all. The results suggest that smooth muscle tone and nerves in the airways could be targets of cationic metals after they dissolve in the lung.