Nitric oxide supports atrial function in sepsis: relevance to side effects of inhibitors in shock.

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 Pharmacol

authors

Price S,Evans TW,Mitchell JA

doi

10.1016/s0014-2999(02)02000-9

keywords:

subject

Has Abstract

pub_date

2002-08-09 00:00:00

pages

279-85

issue

3

eissn

0014-2999

issn

1879-0712

pii

S0014299902020009

journal_volume

449

pub_type

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