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(Hypertension. 2004;44:897.)
© 2004 American Heart Association, Inc.

Scientific Contributions

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

From the Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Correspondence to Toshiro Fujita, MD, Department of Internal Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. E-mail fujita-dis{at}h.u-tokyo.ac.jp

Although Mg²⁺ 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 Mg²⁺ 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; catecholamine release by peripheral sympathetic nerve endings; and the N-type Ca²⁺ channels of cultured neural cells. Intravenous Mg²⁺ infusion (MgSO₄: 3x10^–6 mol/kg body weight/min) induced the greater hypotensive response to hydralazine with attenuated reflex tachycardia in SHRs. In pithed rats, Mg²⁺ infusion significantly attenuated the blood pressure elevation (2±2 mm Hg versus 27±6 mm Hg, P<0.01) in response to spinal electrical stimulation. In the perfused mesenteric arteries system, norepinephrine release was significantly attenuated (51±2%, P<0.01) by high Mg²⁺ concentration solution (4.8 mmol/L) compared with normal Mg²⁺ solution (1.2 mmol/L). When we applied the perforated whole-cell patch clamp method to nerve growth factor-treated PC12 cells, Mg²⁺ blocked voltage-gated Ca²⁺ currents in a concentration-dependent manner. The majority of the voltage-gated Ca²⁺ currents were carried through N-type channels, followed by L-type channels. Mg²⁺ blocked both of these channels. These findings suggest that Mg²⁺ blocks mainly N-type Ca²⁺ channels at nerve endings, and thus inhibits norepinephrine release, which decreases blood pressure independent of its direct vasodilating action.

Key Words: hypertension • catecholamines • ion channels • cocaine

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