Calcineurin inhibitors (CNIs) are effective immunosuppressants used to minimize rejection of transplanted organs and tissues, but they can also cause persistent hypertension and other side effects. Calcineurin is abundantly present in the hypothalamus, which regulates blood pressure, and its inhibition leads to hyperactivity of excitatory NMDA receptors in the brain.
However, long-term blockade of NMDA receptors also comes with negative side effects. To identify a better therapeutic strategy and provide insights into the impact of CNIs on NMDA receptor activity in the hypothalamus, researchers led by Hui-Lin Pan, M.D., Ph.D., examined the role of α2δ-1, a calcium channel subunit. The study showed that CNIs increase NMDA receptor trafficking and activity via interaction with α2δ-1 in the hypothalamus, reinforcing that this is the main driver of CNI-induced hypertension. The findings suggest that α2δ-1 is a viable therapeutic target meriting further research for treating CNI-induced hypertension.