Enhancement of endotoxin-induced vascular hyporeactivity to phenylephrine in the thoracic aortas of Mg-deficient rats ex vivo.
Life Sci
; 73(21): 2713-26, 2003 Oct 10.
Article
em En
| MEDLINE
| ID: mdl-13679239
ABSTRACT
Since endotoxin lethality is enhanced by Mg deficiency in animals, we determined whether endotoxin-induced vascular hyporeactivity to phenylephrine (PE) is enhanced in Mg-deficient rats. Normal and Mg-deficient adult male Wistar rats were injected with Escherichia coli 011 B4 lipopolysaccharide (1 or 5 mg/kg, i.p.). Six h later, rings prepared from their thoracic aortas showed severe hyporeactivity to PE. This was more pronounced in the Mg-deficient rats, and was reversed by in vitro treatment with a highly selective inducible nitric oxide (NO) synthase inhibitor, 1400 W, or a highly selective soluble guanylyl cyclase inhibitor, ODQ. However, reversal required high doses of both inhibitors in Mg-deficient rats. Endotoxemia for 6 h was associated with elevated serum interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha levels, and strong TNF receptor mRNA expression in the abdominal aortas, which were significantly greater in the Mg-deficient rats. Treatment of the thoracic aortas, isolated from control and Mg-deficient rats before endotoxic challenge, with IL-1beta or TNF-alpha for 6 h in vitro caused hyporeactivity to PE, but its severity did not differ significantly between the two groups. These results suggest that high serum IL-1beta and TNF-alpha levels, and increased TNF receptor production in the vascular tissue, contribute to vascular hyporeactivity to PE in endotoxemia, and to its enhancement in Mg-deficient rats, via NO/cGMP signaling.
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Base de dados:
MEDLINE
Assunto principal:
Aorta Torácica
/
Fenilefrina
/
Lipopolissacarídeos
/
Deficiência de Magnésio
/
Músculo Liso Vascular
Limite:
Animals
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article