Magnesium Inhibits Norepinephrine Release by Blocking N-Type Calcium Channels at Peripheral Sympathetic Nerve Endings

T. Shimosawa, K. Takano, K. Ando, T. Fujita
2004 Hypertension  
Although Mg 2ϩ contributes to blood pressure regulation partly in terms of vasodilator action, its sympatholytic effect may also play an important role to control blood pressure. Thus, in the present study, we investigated the effect of Mg 2ϩ on sympathetic tone and blood pressure. We studied its actions on the blood pressure response to hydralazine, a direct vasodilator, in conscious spontaneously hypertensive rats (SHRs), and to electrical stimulation in the pithed Sprague-Dawley rat;
more » ... Dawley rat; catecholamine release by peripheral sympathetic nerve endings; and the N-type Ca 2ϩ channels of cultured neural cells. Intravenous Mg 2ϩ infusion (MgSO 4 : 3ϫ10 Ϫ6 mol/kg body weight/min) induced the greater hypotensive response to hydralazine with attenuated reflex tachycardia in SHRs. In pithed rats, Mg 2ϩ infusion significantly attenuated the blood pressure elevation (2Ϯ2 mm Hg versus 27Ϯ6 mm Hg, PϽ0.01) in response to spinal electrical stimulation. In the perfused mesenteric arteries system, norepinephrine release was significantly attenuated (51Ϯ2%, PϽ0.01) by high Mg 2ϩ concentration solution (4.8 mmol/L) compared with normal Mg 2ϩ solution (1.2 mmol/L). When we applied the perforated whole-cell patch clamp method to nerve growth factor-treated PC12 cells, Mg 2ϩ blocked voltage-gated Ca 2ϩ currents in a concentration-dependent manner. The majority of the voltage-gated Ca 2ϩ currents were carried through N-type channels, followed by L-type channels. Mg 2ϩ blocked both of these channels. These findings suggest that Mg 2ϩ blocks mainly N-type Ca 2ϩ channels at nerve endings, and thus inhibits norepinephrine release, which decreases blood pressure independent of its direct vasodilating action. (Hypertension. 2004;44:897-902.)
doi:10.1161/01.hyp.0000146536.68208.84 pmid:15477382 fatcat:vdcrpjak5vgr3j2rzgue53pzu4