| Magnesium-induced Relaxation in Rat Aorta |
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Sung-suck Oh, Sang-woo Lee, Hyung-sub Kang, Jin-shang Kim |
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Bio-Safety Research Institute, Chonbuk National University |
| Magnesium에 의한 흰쥐 대동맥 이완 |
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오성숙, 이상우, 강형섭, 김진상 |
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전북대학교 생체안전성연구소 |
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| Abstract |
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Magnesium ion ($Mg^{2+}$) is a vasodilator, but little is known about its mechanism of action on vascular system. In vitro, extracellular magnesium sulfate ($MgSO_4$) produced relaxation in phenylephrine (PE) or high KCl-precontracted isolated rat thorocic aorta with (+E) or without (-E) endothelium in a concentration-dependent manner. The $MgSO_4$-induced relaxations were not affected by removal of the endothelium. Pretreatment of +E or -E aortic rings with nitric oxide synthase (NOS) inhibitors ($20{mu}M$ L-NNA, $100{mu}M$ L-NAME, $1{mu}M$ dexamethasone and $400{mu}M$ aminoguanidine), cyclooxygenase inhibitor ($10{mu}M$ indomethacin), guanylate cyclase inhibitors ($10{mu}M$ ODQ and $30{mu}M$ methylene blue) and $Ca^{2+}$ transport blocker ($10{mu}M$ ryanodine) did not affect the relaxant effects of $MgSO_4$. $Ca^{2+}$ channel blockers ($0.3{mu}M$ nifedipine and $0.5{mu}M$ veropamil) completely decreased the relaxant effects of $MgSO_4$ in +E and -E aortic rings. However, in $Ca^{2+}$-free medium, $MgSO_4$-induced vasorelaxation was potentiated and this response was inhibited by nifedipine. Protein kinase C (PKC) inhibitors ($1.0{mu}M$ staurosporine, $0.5{mu}M$ tamoxifen and $0.1{mu}M$ H7) or PLC inhibitor ($100{mu}M$ NCDC) markedly decreased the relaxant effects of $MgSO_4$ in +E and -E aortic rings. In vivo, infusion of $MgSO_4$ elicited significant decreases in arterial blood pressure. After intravenous injection of nifedipine ($150{mu}g/kg$) and NCDC (3 mg/kg), infusion of $MgSO_4$ inhibited the $MgSO_4$-lowered blood pressure markedly. However, after introvenous injection of saponin (15 mg/kg), L-NNA (3 mg/kg), L-NAME (5 mg/kg), indomethacin (2 mg/kg), methylene blue (15 mg/kg) and aminoguanidine (10 mg/kg) failed to inhibit it. These results suggest that endothelial NQ-cGMP or prostaglandin pathway is not involved in vasorelaxant or hypotensive action of $Mg^{2+}$ and that these effects are due to the inhibitory action of $Mg^{2+}$ on the $Ca^{2+}$ channel or PLC-PKC pathway, and are due to the competitive influx of $Mg^{2+}$ and $Ca^{2+}$ through the $Ca^{2+}$ channel. |
| Key Words:
magnesium, relaxant effect, phospholipase C, protein kinase C, aorta |
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