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In Vitro Application of Endotoxin to Thoracic Aortas from Magnesium-Deficient Rats Enhances Vascular Hyporeactivity to Phenylephrine

Department of Veterinary Pharmacology, Faculty of Agriculture, Kagoshima University, Kagoshima, JAPAN

Address reprint requests to: Atsushi Miyamoto, DVM, PhD, Department of Veterinary Pharmacology, Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, JAPAN. E-mail: miyamoto{at}vet.agri.kagoshima-u.ac.jp

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 µg/mL). Contractions to PE were measured with or without an inducible nitric oxide synthase (iNOS) inhibitor (1400W; 0.1 and 1 µM), a guanylate cyclase inhibitor (ODQ; 0.1 and 1 µM), 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 µg/mL), however, there was no significant difference at 0.1, 1 and 10 µg/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 µg/mL). LPS (1 µg/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 µg/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.

Key words: endotoxin, vascular hyporeactivity, iNOS, Mg-deficiency, phenylephrine