Acrolein induces vasodilatation of rodent mesenteric bed via an EDHF-dependent mechanism

Journal Article · Fri Dec 15 04:00:00 EST 2006 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2006.08.008· OSTI ID:20850501

Awe, S O ^[1]; Adeagbo, A S.O. ^[2]; D'Souza, S E ^[2]; Bhatnagar, A ^[1]; Conklin, D J ^[1]

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1. Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, KY 40202 (United States)
2. Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40202 (United States)

Acrolein is generated endogenously during lipid peroxidation and inflammation and is an environmental pollutant. Protein adducts of acrolein are detected in atherosclerotic plaques and neurons of patients with Alzheimer's disease. To understand vascular effects of acrolein exposure, we studied acrolein vasoreactivity in perfused rodent mesenteric bed. Acrolein induced endothelium-dependent vasodilatation that was more robust and more sensitive than dilation induced by 4-hydroxy-trans-2-nonenal, trans-2-hexenal, or propionaldehyde. Acrolein-induced vasodilatation was mediated by K{sup +}-sensitive components, e.g., it was abolished in 0 [K{sup +}]{sub o} buffer or in 3 mM tetrabutylammonium, inhibited 75% in 50 {mu}M ouabain, and inhibited 64% in 20 mM K{sup +} buffer. Moreover, combined treatment with the Ca{sup 2+}-activated K{sup +} channel inhibitors 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34, 100 nM) and apamin (5 {mu}M) significantly reduced vasodilatation without altering sensitivity to acrolein. However, acrolein-induced % dilation was unaffected by L-NAME or indomethacin pretreatment indicating mechanistic independence of NO and prostaglandins. Moreover, acrolein induced vasodilatation in cirazoline-precontracted mesenteric bed of eNOS-null mice confirming eNOS independence. Pretreatment with 6-(2-propargyloxyphenyl) hexanoic acid (PPOH 50 {mu}M), an epoxygenase inhibitor, or the superoxide dismutase mimetic Tempol (100 {mu}M) significantly attenuated acrolein-induced vasodilatation. Collectively, these data indicate that acrolein stimulates mesenteric bed vasodilatation due to endothelium-derived signal(s) that is K{sup +}-, ouabain-, PPOH-, and Tempol-sensitive, and thus, a likely endothelium-derived hyperpolarizing factor (EDHF). These data indicate that low level acrolein exposure associated with vascular oxidative stress or inflammation stimulates vasodilatation via EDHF release in medium-sized arteries - a novel function.

• OSTI ID: 20850501
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 217; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACROLEIN
ARTERIES
BIOLOGICAL STRESS
CALCIUM IONS
ENDOTHELIUM
HEXANOIC ACID
INFLAMMATION
MICE
NERVE CELLS
NERVOUS SYSTEM DISEASES
OUABAIN
PATIENTS
POLLUTANTS
POTASSIUM
POTASSIUM IONS
PROSTAGLANDINS
SENSITIVITY
SUPEROXIDE DISMUTASE
VASODILATION