Aortic hyporeactivity to norepinephrine induced by lipopolysaccharide in cirrhotic rats: Beneficial effects of a non-steroidal anti-inflammatory drugcoupled with a nitric oxide donor

Background and Aims: Cirrhosis is associated with a hyperdynamic syndrome a nd arterial vasodilation that is related to nitric oxide (NO) synthase 3 ov eractivity. Septic shock is frequently associated with cirrhosis and with a vascular induction of NO synthase 2. The aims of this study were to compar e the effects of lipopolysaccharide (LPS) in normal and cirrhotic rats, and to test the effects of a-nonsteroidal anti-inflammatory drug (NSAID) coupl ed with a (NO) donor. Methods: Cirrhotic rats received NO-flurbiprofen, flurbiprofen or vehicle f ollowed by LPS or placebo 15 min later. The heart rate and mean arterial pr essure of rats were monitored for 5 h. Thoracic aortic rings were removed a nd contracted with the use of norepinephrine. Nitric oxide synthase activit y was measured in the aorta and stomach of cirrhotic rats. Results: Arterial pressure decreased in cirrhotic rats in the vehicle/LPS a nd flurbiprofen/LPS groups. After LPS administration, the heart rate of rat s increased in all groups. In the aortic rings, LPS induced hyporeactivity to norepinephrine in ail groups except the NO-flurbiprofen group. This hypo reactivity was abolished after preincubation with N-w-nitro-L-arginine (L-N NA). N-w-nitro-L-arginine had no effect on norepinephrine-induced vasoconst riction in the NO-flurbiprofen/LPS group. Nitric oxide synthase 2 activity in the stomach and aorta of cirrhotic rats was increased in each group exce pt in the NO-flurbiprofen group after LPS administration. Pretreatment with NO-NSAID prevented aortic hyporeactivity to norepinephrine in cirrhotic ra ts treated with LPS as it probably inhibited the NO synthase 2 induction. Conclusions: These findings suggest that NO-flurbiprofen has a beneficial h emodynamic effect in cirrhotic rats and may help to prevent LPS aortic hypo reactivity. (C) 2001 Blackwell Science Asia Pty Ltd.