We examined aldosterone release in response to stimulation with arginine-vasopressin (AVP) using adrenal gland cells. AVP caused a significant increase in aldosterone release from the dispersed adrenal gland cells of wild-type mice (V1AR+/+) at concentrations from 0.1 microM to 1 microM. In contrast, AVP-induced aldosterone release was impaired in adrenal gland cells from mice lacking the vasopressin V1A receptor (V1AR-/-), while adrenocorticotropic hormone (ACTH)-induced aldosterone release in V1AR-/- mice was not significantly different from that in V1AR+/+ mice. In addition, a vasopressin V1A receptor-selective antagonist 1-[1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl]-3,4-dihydro-2(1H)-quinolinone (OPC-21268) potently inhibited AVP-induced aldosterone release. Thus, our study clearly demonstrates that AVP-induced aldosterone release from adrenal gland cells is mediated via the vasopressin V1A receptor in mice.