Calcineurin inhibitors used in clinics – including immunosuppressants for transplant rejection and autoimmune disease treatment – may cause persistent hypertension. Calcineurin inhibitors elevate sympathetic vasomotor activity by decreasing calcineurin activity and potentiating N-methyl-D-aspartate receptor (NMDAR) activity in the hypothalamus. However, how these inhibitors promote NMDAR activity in the hypothalamic paraventricular nucleus to increase sympathetic vasomotor activity remains unknown.