Magnesium inhibits norepinephrine release by blocking N-type calcium channels at peripheral sympathetic nerve endings.
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.
Shimosawa
Tatsuo
T
Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Takano
Koji
K
Ando
Katsuyuki
K
Fujita
Toshiro
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D004558:Electric Stimulation; D006830:Hydralazine / Q000494:pharmacology; D015636:Magnesium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016716:PC12 Cells; D010525:Peripheral Nerves / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D014665:Vasodilator Agents; D015636:Magnesium Chloride; D006830:Hydralazine; D008278:Magnesium Sulfate; D009638:Norepinephrine