Introduction
Excessive NOS activity and NO overproduction are believed to play an important role in sepsis-induced macrocirculatory and microcirculatory dysfunction. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthesis, is extensively metabolised by dimethylarginine dimethylaminohydrolase (DDAH). The DDAH-1 isoform is present in vascular smooth muscle so its inhibition should theoretically reverse sepsis-induced hypotension. We thus investigated the dose-dependent cardiovascular effects of a novel DDAH-1 competitive inhibitor, L-257, in experimental sepsis.