1993 Fiscal Year Final Research Report Summary
Multiple mechanisms for vasodilator effect of magnesium
| Project/Area Number |
03454249
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
FUJITA Toshiro The University of Tokyo, Associate Professor, The Fourth Department of Internal, 医学部(分), 助教授 (10114125)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Katsutoshi Clinical Stuff, The Fourth Department of Internal Medicine, University of Tokyo, 医学部(分), 医員
SHIMOSAWA Tatsuo Clinical Stuff, The Fourth Department of Internal Medicine, University of Tokyo, 医学部(分), 医員 (90231365)
ANDO Katsuyuki Associate, The Fourth Department of Internal Medicine, University of Tokyo, 医学部(分), 助手 (60184313)
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| Project Period (FY) |
1991 – 1993
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| Keywords | magnesium / vascular smooth muscle cells / vascular endothelial cells / vascular reactivity / sympathetic nervous system / angiotensin II |
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| Research Abstract |
Accumulating evidence suggests that deficiency of magnesium (Mg) not only cause hypertension but also accelerates its complication such as ischemic heart disease. These illness should be related to vascular effect of Mg. Mg has been demonstrated to directly dilate vasculature but might affect vascular tone indirectly through the other mechanisms so we examined the effect of Mg deficiency and excess on vascular endothelial and sympathetic nervous function.
(1) 7 week-old Sprague-Dawley (SD) rats was fed on low (3.27mg/100g) and high (87mn/100g) Mg diet for 4 weeks. Mg-deficient rats showed extremely low level of serum Mg compared with Mg-enriched rats. Systolic blood pressure was 130(〕SY.+-.〔)5 mmHg in Mg-dificient rats and 120(〕SY.+-.〔)3 mmHg in Mg-enriched rats (0.05<P<0.1). In intact aortic ring, Potassium (K)-induced contraction was not different between the two groups but maximal contraction (E_<max>) and pD_2 of norepinephrine (NE)-induced contraction was decreased in Mg-deficient
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rats. Endothelial denudation normalized pD_2 of Mg-deficient rats but no E_<max>. Thus, vascular reactivity is suppressed in Mg-deficient rats, which may compensate for the rise in blood pressure due to Mg-deficiency. This effect may at least party be mediated through endothelial function.
(2) We examined the effect of extracellular magnesium on vascular sympathetic nerve activity using the perfusion system of isolated mesenteric artery of SD rats. Sympathetic activity was evaluated as pressor response and increased NE overflow by perivascular electrical stimulation. When Mg concentration in the perfusate was changed from 1.2 mM (normal level) to 0.3 mM, the responses of perfusion pressure and NE overflow by the electrical stimulation was enhanced. On the other hand, high(4.8 mM) Mg decreased it. Thus, Mg inhibits the vascular sympathetic nerve activity. Recently, several investigators including us demonstrated that angiotensin II(ANGII) enhanced the peripheral sympathetic activity. Increased Mg concentration of perfusate, however, suppressed the ANGII-induced enhancement of the sympathetic nervous system. Because ANGII is locally generated in vasculature (for example, endothelial cells), Mg may modify the sympathetic activity through indirect mechanism such as effect on endothelial function as well as its direct action.
In summary, Mg modifies vascular tone through not only the direct action on vascular smooth muscle but also the indirect ones via endothelial cells and sympathetic nerve. Less
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