CHANGES IN THE CONTRACTILE RESPONSES TO CARBACHOL AND IN THE INHIBITORY EFFECTS OF VERAPAMIL AND NITRENDIPINE ON ISOLATED SMOOTH-MUSCLE PREPARATIONS FROM RATS SUBCHRONICALLY EXPOSED TO CO2+ AND NI2+

Male Wistar rats were exposed to subtoxic doses of Co2+ or Ni2+, recei ving Co(NO3)2 or NiSO4 with drinking water for 30 days. No significant differences in the body weight and no visible changes in the behaviou r of the controls and experimental animals were established. Cumulativ e concentration-effect curves for carbachol were obtained in ileum and trachea isolated from control and Co2+- or Ni2+-treated rats. The eff ect of the Ca2+ antagonists on the carbachol-induced contractions was studied by adding increasing concentrations of verapamil or nitrendipi ne to the bath solution 20 min prior to carbachol. The results showed that exposure of rats to subtoxic doses of Co(NO3)2 or NiSO4 altered t he contractile responses to carbachol. The changes in the pD2 values a nd the shift to the left of the concentration-effect curves suggest a higher sensitivity to carbachol in preparations from the ileum of Co2- or Ni2+-exposed rats. The tracheal strips isolated from control and heavy metal-treated rats showed a less potent sensitiveness to carbach ol as compared to the ileal segments. An opposite tendency for decreas ed cholinergic reactivity was observed in tracheal strips from Co2+- a nd Ni2+-treated animals. The inhibitory effect of the Ca2+-antagonists on the contractility of ileal preparations from Co2+-treated rats inc reased at all concentrations of verapamil and at the highest concentra tion of nitrendipine, but decreased at lower concentrations of nitrend ipine. The effect of verapamil on the preparations from Ni2+-exposed r ats was unchanged or even decreased at higher verapamil concentrations . The inhibitory effect of nitrendipine on preparations from Ni2+-expo sed rats decreased at the lowest concentration but increased at the hi ghest concentration of the blocker. In Co2+- or Ni2+-treated tracheal preparations verapamil inhibited the contractions induced by low and m edium concentrations of carbachol but increased the maximal contractil e responses to high concentrations of carbachol.