Effect of cadmium or magnesium on calcium-dependent central function that reduces blood pressure

Abstract

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.

Role of nitric oxide system in hydroxyl radical generation in rat striatum due to carbon monoxide poisoning, as determined by microdialysis

“…It has been shown that calmodulin is required for NOS activity (Bredt, 1999;Heinzel et al, 1992;Ohashi et al, 2007;Wiesinger, 2001). Ohashi et al (2007) demonstrated that the nNOS activity is susceptible to calmodulin antagonists, including W-7, which is used to explore the role of calmodulin in vivo (Hagiwara and Kubo, 2006;Sutoo and Akiyama, 2000). Therefore, we examined the effect of W-7 on the basal and the CO-induced • OH generation, as shown in Fig.…”

“…In addition, d-Arg tended to potentiate the l-NMMA effect, while l-Arg had no effect. To clarify whether or not nNOS is involved in the steady-state • OH generation, we examined the effect of a calmodulin antagonist, W-7, which is used to explore the role of calmodulin in vivo (Hagiwara and Kubo, 2006;Sutoo and Akiyama, 2000), on the steady-state • OH generation, since the calmodulin-dependent nNOS activity is inhibited by W-7 (Ohashi et al, 2007). The calmodulin antagonist had no effect.…”

Blood and Urine Cadmium, Blood Pressure, and Hypertension: A Systematic Review and Meta-analysis

“…Experimental findings suggest that cadmium binds to calcium-binding sites on the regulatory protein calmodulin, and like calcium, cadmium can increase dopamine synthesis in the brain that lowers BP (Sutoo and Akiyama 2000). Further research is merited to investigate this hypothesized MOA in humans.…”

Intracerebroventricular Coadministration of Protoxin-II and Trace Elements in Rats Enhances the Analgesic Effect of the 1.7 Voltage-Gate Sodium Channel Blocker

“…Briefly, the head of the rats was mounted in a stereotactic frame and the soft tissues were incised to expose the skull surface and a small hole was drilled for implantation of the guide cannula. e cannula (23 gauge) was placed into the cerebral ventricle following the protocol designed by Sutoo et al [14]. ICV-cannulated animals were housed in IVCs and allowed to recuperate for 3 days before the experimental procedures were realized.…”

“…Behavioural procedures were performed by a researcher blinded to team and treatment. Considering the principles of the 3Rs (Replacement, Reduction, and Refinement) for performing more humane animal research, we selected the doses of Cd, Mg, and Zn after extensive literature study on the use of trace elements as analgesics or coanalgesics [4][5][6][7][14][15][16][17][18][19][20][21][22][23], and the selection was refined according to Sutoo and Akiyama [14] to obtain optimal balance between efficacy and safety.…”