Mesangial cells are centrally-located glomerular pericytes with contractile, endocrine, and immunity-regulating functions. These cells are thought to maintain normal glomerular function, since mesangial cell proliferation and extracellular matrix formation are hallmarks of chronic glomerular disease. Vasopressin causes mesangial cell contraction, proliferation and hypertrophy. Consequently, the effects of YM218, a potent, nonpeptide vasopressin V1A receptor-selective antagonist, on the growth responses of human mesangial cells to vasopressin were investigated. YM218 showed high affinity for vasopressin V1A receptors, exhibiting a Ki value of 0.18 nM. Vasopressin concentration-dependently increased intracellular Ca2+ levels and induced hyperplasia and hypertrophy in cultured mesangial cells, YM218 potently inhibited these vasopressin-induced responses. These results clearly show that YM218 has both strong affinity for human mesangial cell vasopressin V1A receptors and great potency in inhibiting the vasopressin-induced growth responses of mesangial cells controlled by the vasopressin V1A receptors. The hyperplasia and hypertrophy of mesangial cells in vitro caused by vasopressin indicate its possible in vivo role in glomerular disease pathogenesis. Therefore, YM218 is a potent pharmacologic probe to investigate the physiologic and pathophysiologic roles of vasopressin in the development of renal disease.