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, cob alt, and other metals, can cause interstitial alveolitis, fibrosis, and ast hma in the workplace. Some effects of HM could occur after the metals disso lve in the lung. We examined whether chloride salts of metals in HM alloys can elicit responses or modify reactivity to methacholine (MCh) or response s to electric field stimulation (EFS) in guinea pig tracheal strips. In uns timulated 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 relaxa tion 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+ potentiat ed some responses. The effects of selected metals (10(-6) M; Cr3+, Ni2+, Cd 2+, and Co2+) on EFS-induced contractile and relaxant responses were examin ed (+/-L-MCh; +/- 10(-6) M indomethacin (Indo), 30 min). No metal had any e ffect on the excitatory nonadrenergic, noncholinergic-mediated contraction phase. Cd2+ and Ni2+ inhibited cholinergically mediated contractions of uns timulated strips (+Indo), whereas Cr2+ both inhibited (-MCh, -Indo) and pot entiated (-Indo,+MCh; +Indo, +MCh) contractile responses. Cr3+ was the only metal to inhibit the inhibitory nonadrenergic, noncholinergic-mediated rel axation phase (+/- MCh; -Indo). Co2+ had no effect at all. The results sugg est that smooth muscle tone and nerves in the airways could be targets of c ationic metals after they dissolve in the lung.