Open AccessReduction of blood pressure by store‐operated calcium channel blockers
Author(s) -
Xu YanJun,
Elimban Vijayan,
Dhalla Naranjan S.
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12684
Subject(s) - verapamil , nifedipine , chemistry , endocrinology , medicine , angiotensin ii , extracellular , voltage dependent calcium channel , calcium , vascular smooth muscle , calcium channel , channel blocker , blood pressure , biology , biochemistry , smooth muscle
The voltage‐operated Ca 2+ channels ( VOCC ), which allow Ca 2+ influx from the extracellular space, are inhibited by anti‐hypertensive agents such as verapamil and nifedipine. The Ca 2+ entering from outside into the cell triggers Ca 2+ release from the sarcoplasmic reticulum ( SR ) stores. To refill the depleted Ca 2+ stores in the SR , another type of Ca 2+ channels in the cell membrane, known as store‐operated Ca 2+ channels ( SOCC ), are activated. These SOCC s are verapamil and nifedipine resistant, but are SKF 96465 ( SK ) and gadolinium (Gd 3+ ) sensitive. Both SK and Gd 3+ have been shown to reduce [Ca 2+ ] i in the smooth muscle, but their effects on blood pressure have not been reported. Our results demonstrated that both SK and Gd 3+ 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 Gd 3+ suppressed proliferation of vascular smooth muscle cells in the absence or presence of lysophosphatidic acid ( LPA ). SK decreased the elevation of [Ca 2+ ] i induced by LPA , endothelin‐1 ( ET ‐1) and angiotensin II (Ang II), but did not affect the norepinephrine ( NE )‐evoked increase in [Ca 2+ ] i . On the other hand, Gd 3+ inhibited the LPA and Ang II induced change in [Ca 2+ ] i , but had no effect on the ET ‐1 and NE induced increase in [Ca 2+ ] i . The combination of verapamil and SK abolished the LPA ‐ or adenosine‐5′‐triphosphate (ATP)‐induced [Ca 2+ ] i augmentation. These results suggest that SOCC inhibitors, like VOCC blocker, may serve as promising drugs for the treatment of hypertension.