Iwamoto Takahiro, Kita Satomi
Department of Pharmacology, School of Medicine, Fukuoka University, Japan.
J Pharmacol Sci. 2006 Sep;102(1):32-6. doi: 10.1254/jphs.fmj06002x6. Epub 2006 Sep 8.
Excess salt intake is a major risk factor for hypertension. However, the molecular mechanisms underlying salt-dependent hypertension remain obscure. Our recent studies using selective Na(+)/Ca(2+) exchange inhibitors and genetically engineered mice provide compelling evidence that salt-dependent hypertension is triggered by Ca(2+) entry through Na(+)/Ca(2+) exchanger type 1 (NCX1) in arterial smooth muscle. Endogenous cardiac glycosides, which may contribute to salt-dependent hypertension, seem to be necessary for NCX1-mediated hypertension. Intriguingly, recent studies by Dostanic-Larson et al. using knock-in mice with modified cardiac glycoside binding affinity of Na(+),K(+)-ATPases demonstrate that this binding site plays an important physiological role in blood pressure control. Thus, when cardiac glycosides inhibit Na(+),K(+)-ATPase in arterial smooth muscle cells, the elevation of local Na(+) on the submembrane area is believed to facilitate Ca(2+) entry through NCX1, resulting in vasoconstriction. This proposed pathway may have enabled us to explain how to link dietary salt to hypertension.
过量摄入盐是高血压的主要危险因素。然而，盐依赖性高血压背后的分子机制仍不清楚。我们最近使用选择性钠/钙交换抑制剂和基因工程小鼠进行的研究提供了令人信服的证据，表明盐依赖性高血压是由动脉平滑肌中通过1型钠/钙交换体（NCX1）的钙内流引发的。内源性强心苷可能促成盐依赖性高血压，似乎是NCX1介导的高血压所必需的。有趣的是，多斯塔尼克-拉尔森等人最近使用具有改变的强心苷与钠钾ATP酶结合亲和力的敲入小鼠进行的研究表明，该结合位点在血压控制中起重要的生理作用。因此，当强心苷抑制动脉平滑肌细胞中的钠钾ATP酶时，细胞膜下区域局部钠的升高被认为会促进钙通过NCX1内流，导致血管收缩。这一提出的途径可能使我们能够解释饮食中的盐与高血压之间的联系。
