Translational potential of targeting Anoctamin-1-Encoded Calcium-Activated chloride channels in hypertension.

Calcium-activated chloride channels (CaCC) provide a depolarizing stimulus to a variety of tissues through chloride efflux in response to a rise in internal Ca2+ and voltage. One of these channels, Anoctamin-1 (ANO1 or TMEM16A) is now recognized to play a central role in promoting smooth muscle tone in various types of blood vessels. Its role in hypertension, and thus the therapeutic promise of targeting ANO1, is less straightforward. This review gives an overview of our current knowledge about the potential role ANO1 may play in hypertension within the systemic, portal, and pulmonary vascular systems and the importance of this information when pursuing potential treatment strategies. While the role of ANO1 is well-established in several forms of pulmonary hypertension, its contributions to both the generation of vascular tone and its role in hypertension within the systemic and portal systems are much less clear. This, combined with ANO1's various roles throughout a multitude of tissues throughout the body, command caution when targeting ANO1 as a therapeutic target and may require tissue-selective strategies.