The effect of intracerebroventricular (i.c.v.) administration of cadmium or magnesium on central calcium-dependent blood pressure regulation was investigated. The systolic blood pressure of spontaneously hypertensive rats (SHR; male, 13 weeks of age) decreased following i.c.v. administration of cadmium chloride (20 nmol/rat), and increased following i.c.v. administration of magnesium chloride (20, 600, and 1,200 nmol/rat). The hypotensive effect of cadmium was suppressed by i.c.v. administration of W-7 (a calmodulin antagonist, 30 microg/rat). Taking into consideration these results with our previous reports, it is suggested that cadmium binds to the calcium-binding sites of calmodulin and activates calcium/calmodulin-dependent enzymes in a disorderly manner, whereas magnesium does not. Therefore, cadmium increases dopamine synthesis in the brain via a calmodulin-dependent system, and the resultant increase in dopamine levels inhibits sympathetic nerve activity and reduces blood pressure in SHR.