Disruption of vascular Ca^sup 2+^-activated chloride currents lowers blood pressure

High blood pressure is the leading risk factor for death worldwide. One of the hallmarks is a rise of peripheral vascular resistance, which largely depends on arteriole tone. Ca^sup 2+^-activated chloride currents (CaCC) in vascular smooth muscle cells (VSMC) are candidates for increasing vascular contractility. Researchers have analyzed the vascular tree and identified substantial CaCCs in VSMCs of the aorta and carotid arteries. CaCCs were small or absent in VSMCs of medium-sized vessels such as mesenteric arteries and larger retinal arterioles. In small vessels of the retina, brain, and skeletal muscle, where contractile intermediate cells or pericytes gradually replace VSMCs, CaCCs were particularly large. Targeted disruption of the calcium-activated chloride channel TMEM16A, also known as ANO1, in VSMCs, intermediate cells, and pericytes eliminated CaCCs in all vessels studied. Mice lacking vascular TMEM16A had lower systemic blood pressure and a decreased hypertensive response following vasoconstrictor treatment. Their data suggest that, TMEM16A plays a general role in arteriolar and capillary blood flow and is a promising target for the treatment of hypertension.