Effect of cadmium or magnesium on calcium-dependent central function that reduces blood pressure.
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.
Sutoo
D
D
Institute of Medical Science, University of Tsukuba, Japan. dsutoo@md.tsukuba.ac.jp
Akiyama
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002104:Cadmium / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007223:Infant; D007276:Injections, Intraventricular; D008274:Magnesium / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013449:Sulfonamides / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013449:Sulfonamides; D002104:Cadmium; C017967:W 7; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D008274:Magnesium; D002118:Calcium