cGMP levels in chronic cadmium disease and osteoarthritis

To investigate the effect of cadmium on guanyl cyclase activity, urine levels of the nucleotide cGMP were measured in patients with bone and renal lesions resulting from chronic cadmium exposure, in patients with osteoarthritis and in a normal age-matched control population. The effects of cadmium, zinc and mercury salts on blood mononuclear cell cGMP production were also studied in vitro. The two patient groups exhibited clear differences in cGMP excretion. Lower urine cGMP (59%, P less than 0.01) and creatinine values (43%, P less than 0.01) were found in cadmium-exposed patients and higher cGMP values (56%, P less than 0.05) in patients with osteoarthritis, compared to the control group. Creatinine adjusted cGMP values were also lower in cadmium-exposed patients (28%, P less than 0.05) and higher in patients with osteoarthritis (130%, P less than 0.01). In vitro, a 10 h exposure of mononuclear cells to cadmium or mercury salts depressed guanyl cyclase activity in most experiments. At 10(-4) M, mercury was consistently more inhibitory in all cultures (95%, P less than 0.01). As cadmium has a potential for inhibiting guanyl cyclase activity in human tissue, the low urine cGMP values found in patients with cadmium disease may be attributable to chronic cadmium exposure. High guanyl cyclase activity in patients with osteoarthritis may be associated with inflammation.