Acrolein generation stimulates hypercontraction in isolated human blood vessels
Journal Article
·
· Toxicology and Applied Pharmacology
- Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, KY 40202 (United States) and Department of Biology, University of Wisconsin-Eau Claire, Eau Claire, WI 54701 (United States)
- Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, KY 40202 (United States)
- Department of Biology, University of Wisconsin-Eau Claire, Eau Claire, WI 54701 (United States)
- Department of Cardiothoracic Surgery, Luther Hospital/Midelfort Clinic, Eau Claire, WI 54702 (United States)
- Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106 (United States)
- Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555-0609 (United States)
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 H{sub 2}O{sub 2} exposure (1 {mu}M-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 {mu}M), (3) the vasoactive effects of two other SSAO amine substrates, benzylamine and methylamine, and (4) the contribution of extracellular Ca{sup 2+} to hypercontraction. Acrolein or allylamine but not H{sub 2}O{sub 2}, 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 Ca{sup 2+}-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.
- OSTI ID:
- 20850502
- 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
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