理论上是可行的，需要解决抑制剂的特异性问题，以减少负作用。治疗高血压的药物已经很多了，前景如何难以预测。

http://onlinelibrary.wiley.com/doi/10.1111/jcmm.12684/full

J Cell Mol Med. 2015 Oct 16. doi: 10.1111/jcmm.12684. [Epub ahead of print]

Reduction of blood pressure by store-operated calcium channel blockers.

Xu YJ¹, Elimban V¹, Dhalla NS¹.

Author information

• ¹Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, Department of Physiology and Pathophysiology, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.

Abstract

The voltage-operated Ca²⁺ channels (VOCC), which allow Ca²⁺ influx from the extracellular space, are inhibited by anti-hypertensive agents such as verapamil and nifedipine. The Ca²⁺ entering from outside into the cell triggers Ca²⁺ release from the sarcoplasmic reticulum (SR) stores. To refill the depleted Ca²⁺ stores in the SR, another type of Ca²⁺ channels in the cell membrane, known as store-operated Ca²⁺ channels (SOCC), are activated. These SOCCs are verapamil and nifedipine resistant, but are SKF 96465 (SK) and gadolinium (Gd³⁺ ) sensitive. Both SK and Gd³⁺ have been shown to reduce [Ca²⁺ ]_i in the smooth muscle, but their effects on blood pressure have not been reported. Our results demonstrated that both SK and Gd³⁺ produced a dose-dependent reduction in blood pressure in rat. The combination of SK and verapamil produced an additive action in lowering the blood pressure. Furthermore, SK, but not Gd³⁺ suppressed proliferation of vascular smooth muscle cells in the absence or presence of lysophosphatidic acid (LPA). SK decreased the elevation of [Ca²⁺ ]_i induced by LPA, endothelin-1 (ET-1) and angiotensin II (Ang II), but did not affect the norepinephrine (NE)-evoked increase in [Ca²⁺ ]_i . On the other hand, Gd³⁺ inhibited the LPA and Ang II induced change in [Ca²⁺ ]_i , but had no effect on the ET-1 and NE induced increase in [Ca²⁺ ]_i . The combination of verapamil and SK abolished the LPA- or adenosine-5'-triphosphate (ATP)-induced [Ca²⁺ ]_i augmentation. These results suggest that SOCC inhibitors, like VOCC blocker, may serve as promising drugs for the treatment of hypertension.

© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

KEYWORDS:

Ca2+ antagonists; antihypertensive agents; cell proliferation; hypertension; intracellular Ca2+

PMID:

26471725

[PubMed - as supplied by publisher]

 

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