Regulation of the expression of the klotho gene, which suppresses the expression of multiple aging-associated phenotypes, by angiotensin II was investigated. Continuous infusion of angiotensin II downregulated renal klotho gene expression, which was an AT1 receptor-dependent, but pressor-independent event. In some experiments, adenovirus harboring mouse klotho gene(ad-klotho, 3.3 x 10(10) pfu) was intravenously administered immediately before starting angiotensin II infusion, and this resulted in an improvement of creatinine clearance, decrease in urinary protein excretion, and amelioration of tubulointerstitial damage induced by this octapeptitde. Downregulation of the renal klotho gene may have a role in the development of angiotensin II-induced end organ damage.