Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-4-27
pubmed:abstractText
A newly discovered antifungal agent, pramanicin, within the therapeutically effective concentration range (4-100 microM), inhibits the tone of phenylephrine (PE)-precontracted dog carotid arterial rings in a concentration-dependent manner and leads to gradual development of relaxation. However, pramanicin had no effect on rings precontracted with 100 mM KCl or on endothelium-denuded rings. Thus, inhibition by pramanicin of PE-induced contraction was endothelium-dependent. Preincubation of 100 microM pramanicin with carotid arterial rings for 30 min did not significantly affect the concentration-contraction response to PE, but almost completely inhibited the endothelium-dependent relaxation response to subsequent addition of 3 microM carbachol or 100 microM pramanicin. This irreversible inhibition of endothelium-dependent relaxation, which is independent of extracellular Ca2+, suggests possible endothelial cell damage by pramanicin. Pretreatment of the endothelium-intact vascular rings with L-N(G)-nitro-arginine (100 microM) inhibited the relaxation of PE-precontracted rings induced by 3 microM carbachol or 100 microM pramanicin, suggesting that the generation of nitric oxide (NO) in endothelial cells mediates the slow vascular relaxation induced by pramanicin. We conclude that pramanicin has little direct effect on the contractility of smooth muscle cells, but causes an initial slow endothelium-dependent, NO-mediated vascular relaxation. This is followed by a cytotoxic effect on vascular endothelial cells, eventually resulting in the loss of vasorelaxant function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-5198
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
234-40
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11325015-Animals, pubmed-meshheading:11325015-Antifungal Agents, pubmed-meshheading:11325015-Carbachol, pubmed-meshheading:11325015-Carotid Arteries, pubmed-meshheading:11325015-Dogs, pubmed-meshheading:11325015-Endothelium, Vascular, pubmed-meshheading:11325015-Enzyme Inhibitors, pubmed-meshheading:11325015-Epoxy Compounds, pubmed-meshheading:11325015-Female, pubmed-meshheading:11325015-Isometric Contraction, pubmed-meshheading:11325015-Lactams, pubmed-meshheading:11325015-Male, pubmed-meshheading:11325015-Muscle, Smooth, Vascular, pubmed-meshheading:11325015-Nitric Oxide Synthase, pubmed-meshheading:11325015-Phenylephrine, pubmed-meshheading:11325015-Vasoconstrictor Agents, pubmed-meshheading:11325015-Vasodilation, pubmed-meshheading:11325015-Vasodilator Agents, pubmed-meshheading:11325015-omega-N-Methylarginine
pubmed:year
2001
pubmed:articleTitle
Vasorelaxant effects of pramanicin, an anti-fungal agent: selective action on endothelial cells.
pubmed:affiliation
Department of Medicine, Faculty of Health Sciences, Faculty of Science, McMaster University, Hamilton, Ontario, Canada. kwancy@mcmaster.ca
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't