Abstract:
:The mechanisms underlying myocardial dysfunction in sepsis remain poorly understood. The theoretical benefits of nitric oxide synthase (NOS) inhibition in reversing the haemodynamic changes that characterise septic shock have not been supported by clinical trials, some of which have demonstrated detrimental myocardial effects. We have therefore assessed the effects of endotoxaemia on NOS enzyme expression as well as a number of functional responses of myocardial tissue from rats. Atrial tissue expressed high levels of mRNA for inducible (i) NOS and released increased levels of nitrite after animals were treated with endotoxin. In parallel, the inotropic response stimulated by isoprenaline was reduced in atria from endotoxin-treated animals, an effect that was reversed when endogenous release of NO was maximised. Our results suggest that myocardial contractility is maintained by NO production and that inhibitors may compromise cardiac output; this may explain the deleterious effects of NOS inhibition on cardiac function in clinical trials.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Price S,Evans TW,Mitchell JAdoi
10.1016/s0014-2999(02)02000-9keywords:
subject
Has Abstractpub_date
2002-08-09 00:00:00pages
279-85issue
3eissn
0014-2999issn
1879-0712pii
S0014299902020009journal_volume
449pub_type
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