Effects of magnesium on prostacyclin synthesis and intracellular free calcium concentration in vascular cells.
This study investigated the effects of extracellular magnesium concentration ([Mg2+]e; 0.3-3 mM) on intracellular free calcium concentration ([Ca2+]i) and prostacyclin (PGI2) production in cultured human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells from rats (VSMC) under basal and agonist-stimulated conditions. We used histamine as agonist which increases [Ca2+]i and PGI2 production in HUVEC, norepinephrine in VSMC. [Mg2+]e dose-dependently increased basal and agonist-stimulated PGI2 production in both cells. [Mg2+]e dose-dependently reduced basal [Ca2+]i in VSMC, but did not influence in HUVEC. In both cells, increasing [Mg2+]e reduced agonist-stimulated [Ca2+]i responses. Furthermore, [Mg2+]e dose-dependently reduced agonist-stimulated [Ca2+]i in Ca(2+)-free buffer, indicating intracellular Ca2+ release. In VSMC, 10(-6) M diltiazem and 10(-7) M nifedipine, Ca2+ channel blockers, reduced agonist-stimulated [Ca2+]i as well as 3 mM Mg2+, but did not affect PGI2 production. [Mg2+]e amplified dose-dependently arachidonic acid-induced PGI2 production in both cells, suggesting the activation of cyclooxygenase and/or PGI2 synthetase. Our results suggest that [Mg2+]e influences intracellular Ca2+ mobilization of not only vascular smooth muscle cells but also endothelial cells by inhibiting both Ca2+ influx and intracellular Ca2+ release. [Mg2+]e enhances PGI2 production in both types of cells, although the mechanism is likely to be independent from Ca2+ mobilization.
Satake
Kazuo
K
First Department of Internal Medicine, Fukui University, 23 Shimoaizuki, Matsuokacho, Fukui 910-1193, Japan.
Lee
Jong-Dae
JD
Shimizu
Hiromasa
H
Uzui
Hiroyasu
H
Mitsuke
Yasuhiko
Y
Yue
Hong
H
Ueda
Takanori
T
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis* / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008278:Magnesium Sulfate / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D044062:Prostaglandins I / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D044062:Prostaglandins I; D016718:Arachidonic Acid; D008278:Magnesium Sulfate; D006632:Histamine; D011464:Epoprostenol; D008274:Magnesium; D002118:Calcium; D009638:Norepinephrine