Drugs were administered to ischemic-induced Acute Renal Failure (ARF) rats 5 minutes before the start of ischemia. A selective histamine H3 receptor antagonist, thioperamide (30 nmol/rat i.c.v.), which was given 10 minutes before the ischemia, eliminated the preventing effects by L-carnosine (15 nmol/rat i.v.) on ischemic ARF. In contrast, a selective H3 receptor agonist, R-methylhistamine (5 pmol/rat i.c.v.), prevented the I/R-induced Renal Injury as well as L-carnosine (5 pmol/rat) did. Here, HRH3 is linked to ischemia.