title: Chemical-induced vasculature injury. Summary of the symposium presented at the 32nd annual meeting of the Society of Toxicology, New Orleans, Louisiana, March 1993.
abstract: The cross-sectional structure of the vasculature is comparatively simple, comprising three layers--the intima, adjacent to the lumen, the media, and the adventitia. Notwithstanding this simplicity, the vessels are host to a variety of reactions to injury. Two cell types, endothelial cells of the intima and smooth muscle cells of the media, are principal targets of damage and repair. The endothelial cells of the intimal layer of the vessel wall present a macromolecular barrier and are important in maintaining vessel integrity. When the integrity is compromised by physical or chemical injury, endothelial cells play a key role in the repair processes. The use of single-cell wound models allows the mechanisms of damage and subsequent repair to be studied in depth. Repair processes can be observed using time-lapse photography and differences between cytoskeleton changes during repair and reendothelialization of small and large wounds can be discriminated. In rats treated with the plant toxin monocrotaline, pulmonary vascular injury occurs which manifests as thrombosis and remodeling with consequent progressive pulmonary hypertension. In vivo and in vitro studies of the mechanism of monocrotaline toxicity suggest that the endothelial cells are an important target. In vitro studies show monocrotaline to be directly cytotoxic; in cells that survive, there are functional changes to the endothelial cells, resulting in a decreased repair capability which may lead to the complex, progressive lung lesions that develop. The other target cells of the vasculature are the smooth muscle cells of the media. Ingestion of primary amines allylamine and beta-aminopropionitrile (beta-APN) results in chronic vasculotoxicity to the aorta and medium-sized arteries. For allylamine, subtle changes in smooth muscle result in medial hypertrophy and subintimal proliferation. The changes are slow to occur, taking weeks or months of repeated treatment. For beta-APN, which is the active ingredient of the toxic sweet pea Lathyrus odoratous, vascular toxicity is manifested by fatal rupture of aortic aneurysms. When these agents are administered concomitantly, a synergistic acute smooth muscle necrosis occurs in large elastic arteries and degenerative changes are seen in muscular arteries. A change in the target for toxicity of allylamine toward the vasculature may be responsible for this synergistic toxic insult. Medial smooth muscle necrosis is also noteworthy after administration of certain pharmaceutical agents of diverse structure and pharmacological activity. These agents induce arteriopathies in dogs and rats, although at different sites. In dogs, the coronary arteries are susceptible, whereas in rats the mesenteric arteries are the principal sites of injury.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston 77555-0605, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Boor
authors.forename: A I
authors.initials: AI
authors.lastname: Gotlieb
authors.forename: E C
authors.initials: EC
authors.lastname: Joseph
authors.forename: W D
authors.initials: WD
authors.lastname: Kerns
authors.forename: R A
authors.initials: RA
authors.lastname: Roth
authors.forename: K E
authors.initials: KE
authors.lastname: Tomaszewski
mesh_terms: D000588:Amines / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000293:injuries; D004730:Endothelium, Vascular / Q000033:anatomy & histology / Q000293:injuries* / Q000502:physiology; D008168:Lung / Q000098:blood supply / Q000187:drug effects*; D016686:Monocrotaline / Q000031:analogs & derivatives* / Q000633:toxicity; D012038:Regeneration / Q000502:physiology; D017540:Tunica Media / Q000293:injuries*; D014947:Wounds and Injuries / Q000139:chemically induced*
chemical_list: D000588:Amines; C014114:monocrotaline pyrrole; D016686:Monocrotaline