ITPR1 and Hypertension: Although the IP3Rs (IP3R1, 2, and 3) have been previously reported to modulate Ca2+ release and regulate vascular contractility in hypertension (12), to our knowledge, this is the first study that dissects the role of the VSMC IP3R1 and its direct link to the neurohormonal dysregulation in HF using human aortic tissues and IP3R1VSMC–/– mice.