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Titolo:
Regional changes in constitutive nitric oxide synthase and the hemodynamicconsequences of its inhibition in lipopolysaccharide-treated pigs
Autore:
Javeshghani, D; Magder, S;
Indirizzi:
McGill Univ, Royal Victoria Hosp, Crit Care Div, Hlth Ctr,Dept Med, Montreal, PQ H3A 1A1, Canada McGill Univ Montreal PQ Canada H3A 1A1 Med, Montreal, PQ H3A 1A1, Canada McGill Univ r, Royal Victoria Hosp, Crit Care Div, Dept Physiol,Hlth Ctr, Montreal, PQ H3A 1A1, Canada McGill Univ r Montreal PQ Canada H3A 1A1 tr, Montreal, PQ H3A 1A1, Canada Meakins Christie Labs, Montreal, PQ, Canada Meakins Christie Labs Montreal PQ Canada stie Labs, Montreal, PQ, Canada
Titolo Testata:
SHOCK
fascicolo: 3, volume: 16, anno: 2001,
pagine: 232 - 238
SICI:
1073-2322(200109)16:3<232:RCICNO>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; ARTERY ENDOTHELIAL-CELLS; SMOOTH-MUSCLE CELLS; MOLECULAR-CLONING; MESSENGER-RNA; PORCINE ENDOTOXEMIA; GENE-EXPRESSION; SEPSIS; PEROXYNITRITE; SUPEROXIDE;
Keywords:
sepsis; cardiac output; nitric oxide; venous resistance; pulmonary artery;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Magder, S McGill Univ, Royal Victoria Hosp, Crit Care Div, Hlth Ctr,Dept Med, 687 Pine Ave W, Montreal, PQ H3A 1A1, Canada McGill Univ 687 Pine Ave WMontreal PQ Canada H3A 1A1 A1, Canada
Citazione:
D. Javeshghani e S. Magder, "Regional changes in constitutive nitric oxide synthase and the hemodynamicconsequences of its inhibition in lipopolysaccharide-treated pigs", SHOCK, 16(3), 2001, pp. 232-238

Abstract

The role of constitutive nitric oxide synthases (cNOS) in sepsis remains controversial. Part of the problem is that many of the studies have been performed in rats, which respond differently than larger animals. Our objective, therefore, was to determine whether cNOS, i.e. ecNOS (NOS-3) and nNOS (NOS-1) are still active in vessels of pigs treated with lipopolysaccharide (LPS) from Escherichia coli. We also characterized the dose-response relationship of the NOS inhibitor N-G-nitro-L-arginine-methyl-ester (L-NAME) in the arterial, venous, and pulmonary circuits as a reflection of NO production. We anesthetized and ventilated 14 pigs, which were instrumented for hemodynamic measurements. We measured mean circulatory filling pressure and resistance to venous return by transiently arresting the circulation with a balloon in the right atrium. Animals were given 20 mug/kg of LPS (n = 8) or saline (n = 6) over 2 h. They were then given progressively increasing doses of L-NAME (0.5 to 16 mug/kg). We injected 20 pg boluses of norepinephrine at baseline, after 2 h, and after 0.5, 4, and 16 pg of L-NAME to test the pressor response. Tissue was obtained from six control animals followed for 2h, eight animals treated with LIPS for 2 h and then sacrificed, and four animals treated for 2 h and sacrificed after 2 more h. Cardiac output did not change, and the systemic vascular resistance fell in LPS animals. By Western analysis, ecNOS was increased in LPS animals at 2 and 4 h in the aorta and vena cava, and this was paralleled by changes in nNOS in the vena cava. In contrast, ecNOS decreased in the pulmonary artery and nNOS did not change. Calcium-dependent NOS activity increased with LPS in the aorta and venacava but decreased in pulmonary artery at 4 h. The dose-response relationships to L-NAME for systemic vascular resistance, resistance to venous return, and cardiac output were shifted to the left after LPS in support of increased sensitivity supporting increased NO. The pressor response to norepinephrine was depressed after LPS and was partially restored with 4 mg/kg of L-NAME, but this dose produced 90% of the fall in cardiac output. In conclusion, in contrast to rats, cNOS activity is present in the systemic vessels of LPS-treated pigs and could play a role in the pathophysiology of sepsis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 20:00:01