Acrolein generation stimulates hypercontraction in isolated human blood vessels

D. J. Conklin, A. Bhatnagar, H. R. Cowley, G. H. Johnson, R. J. Wiechmann, L. M. Sayre, M. B. Trent, P. J. Boor

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Increased risk of vasospasm, a spontaneous hyperconstriction, is associated with atherosclerosis, cigarette smoking, and hypertension-all conditions involving oxidative stress, lipid peroxidation, and inflammation. To test the role of the lipid peroxidation- and inflammation-derived aldehyde, acrolein, in human vasospasm, we developed an ex vivo model using human coronary artery bypass graft (CABG) blood vessels and a demonstrated acrolein precursor, allylamine. Allylamine induces hypercontraction in isolated rat coronary artery in a semicarbazide-sensitive amine oxidase activity (SSAO) dependent manner. Isolated human CABG blood vessels (internal mammary artery, radial artery, saphenous vein) were used to determine: (1) vessel responses and sensitivity to acrolein, allylamine, and H2O2 exposure (1 μM-1 mM), (2) SSAO dependence of allylamine-induced effects using SSAO inhibitors (semicarbazide, 1 mM; MDL 72274-E, active isomer; MDL 72274-Z, inactive isomer; 100 μM), (3) the vasoactive effects of two other SSAO amine substrates, benzylamine and methylamine, and (4) the contribution of extracellular Ca2+ to hypercontraction. Acrolein or allylamine but not H2O2, benzylamine, or methylamine stimulated spontaneous and pharmacologically intractable hypercontraction in CABG blood vessels that was similar to clinical vasospasm. Allylamine-induced hypercontraction and blood vessel SSAO activity were abolished by pretreatment with semicarbazide or MDL 72274-E but not by MDL 72274-Z. Allylamine-induced hypercontraction also was significantly attenuated in Ca2+-free buffer. In isolated aorta of spontaneously hypertensive rat, allylamine-induced an SSAO-dependent contraction and enhanced norepinephrine sensitivity but not in Sprague-Dawley rat aorta. We conclude that acrolein generation in the blood vessel wall increases human susceptibility to vasospasm, an event that is enhanced in hypertension.

Original languageEnglish (US)
Pages (from-to)277-288
Number of pages12
JournalToxicology and Applied Pharmacology
Volume217
Issue number3
DOIs
StatePublished - Dec 15 2006

Keywords

  • Aldehydes
  • Allylamine
  • Amine oxidase
  • EC 1.4.3.6
  • HO
  • Hypertension
  • Vasospasm

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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  • Cite this

    Conklin, D. J., Bhatnagar, A., Cowley, H. R., Johnson, G. H., Wiechmann, R. J., Sayre, L. M., Trent, M. B., & Boor, P. J. (2006). Acrolein generation stimulates hypercontraction in isolated human blood vessels. Toxicology and Applied Pharmacology, 217(3), 277-288. https://doi.org/10.1016/j.taap.2006.09.009