Excess L-arginine restores endothelium-dependent relaxation impaired by monocrotaline pyrrole

Journal Article · Thu Sep 15 04:00:00 EDT 2005 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2005.01.002· OSTI ID:20721992

Wei, Cheng ^[1]; Oike, Masahiro ^[1]; Hirakawa, Masakazu ^[1]; Ohnaka, Keizo ^[2]; Koyama, Tetsuya ^[1]; Ito, Yushi ^[1]

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1. Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-82 (Japan)
2. Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-82 (Japan)

The pyrrolizidine alkaloid plant toxin monocrotaline pyrrole (MCTP) causes pulmonary hypertension in experimental animals. The present study aimed to examine the effects of MCTP on the endothelium-dependent relaxation. We constructed an in vitro disease model of pulmonary hypertension by overlaying MCTP-treated bovine pulmonary artery endothelial cells (CPAEs) onto pulmonary artery smooth muscle cell-embedded collagen gel lattice. Acetylcholine (Ach) induced a relaxation of the control CPAEs-overlaid gels that were pre-contracted with noradrenaline, and the relaxation was inhibited by L-NAME, an inhibitor of NO synthase (NOS). In contrast, when MCTP-treated CPAEs were overlaid, the pre-contracted gels did not show a relaxation in response to Ach in the presence of 0.5 mM L-arginine. Expression of endothelial NOS protein, Ach-induced Ca{sup 2+} transients and cellular uptake of L-[{sup 3}H]arginine were significantly smaller in MCTP-treated CPAEs than in control cells, indicating that these changes were responsible for the impaired NO production in MCTP-treated CPAEs. Since cellular uptake of L-[{sup 3}H]arginine linearly increased according to its extracellular concentration, we hypothesized that the excess concentration of extracellular L-arginine might restore NO production in MCTP-treated CPAEs. As expected, in the presence of 10 mM L-arginine, Ach showed a relaxation of the MCTP-treated CPAEs-overlaid gels. These results indicate that the impaired NO production in damaged endothelial cells can be reversed by supplying excess L-arginine.

• OSTI ID: 20721992
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 207; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACETYLCHOLINE
ALKALOIDS
ARGININE
ARTERIES
CALCIUM IONS
CATTLE
COLLAGEN
ENDOTHELIUM
GELS
HYPERTENSION
IN VITRO
NITRIC OXIDE
NORADRENALINE
PLANTS
PYRROLES
RELAXATION
TOXINS
TRITIUM