In vitro application of endotoxin to thoracic aortas from magnesium-deficient rats enhances vascular hyporeactivity to phenylephrine.
OBJECTIVE
Endotoxin-induced vascular hyporeactivity to phenylephrine (PE) is well described in rat aortas, but has not been investigated in those from magnesium (Mg)-deficient rats in vitro.


METHODS
Segments of thoracic aorta from control and Mg-deficient rats were incubated in culture medium for 6 hours in the presence or absence of bacterial lipopolysaccharide (LPS; 0.001-10 microg/mL). Contractions to PE were measured with or without an inducible nitric oxide synthase (iNOS) inhibitor (1400W; 0.1 and 1 microM), a guanylate cyclase inhibitor (ODQ; 0.1 and 1 microM), or a potassium channel inhibitor (TEA; 1 and 10 mM).


RESULTS
LPS induced hyporeactivity in a concentration-dependent manner under relatively low concentrations (0.001-0.1 microg/mL), however, there was no significant difference at 0.1, 1 and 10 microg/mL. LPS-induced hyporeactivity was not significantly affected by endothelium-denudation. The hyporeactivity was enhanced in thoracic aortas from Mg-deficient rats by LPS (0.01, 0.1 and 1 microg/mL). LPS (1 microg/mL) induced hyporeactivity was reversed with 1400W, ODQ or TEA in both aortas in a concentration-dependent manner, however the degree of reversal was weaker in the Mg-deficient rat aorta than in the control rat one. iNOS mRNA level was increased by LPS (0.1 microg/mL) and the increment was significantly high in Mg-deficient rat thoracic aorta.


CONCLUSIONS
From these results it is clearly demonstrated that LPS-induced vascular hyporeactivity to PE is enhanced in thoracic aorta from Mg-deficient rats, and it is suggested that LPS-induced NO production might contribute to the enhancement via stimulation of NO-cyclic GMP-potassium channel pathway.
Department of Veterinary Pharmacology, Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan. miyamoto@vet.agri.kagoshima-u.ac.jp
Atsushi
A
Miyamoto
Hiroshi
H
Moriki
Shigeru
S
Ishiguro
Akira
A
Nishio
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology*; D008275:Magnesium Deficiency / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009924:Organ Culture Techniques; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D007527:Isoenzymes; D008070:Lipopolysaccharides; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D008274:Magnesium