Linked Life Data

9495823

Source:http://linkedlifedata.com/resource/pubmed/id/9495823

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-3-27
pubmed:abstractText
Organic nitrates undergo enzymatic metabolization in the vasculature to release the active compound nitric oxide (NO). The resulting preferential venodilation has been suggested to be related to the vascular bioactivation process of organic nitrates because sodium nitroprusside, which is bioactivated differently, is not venoselective. We sought to determine whether NO has an influence on vascular bioconversion of organic nitrates because endogenous endothelial production of NO is smaller in veins than in arteries. Rings of porcine coronary arteries were subjected to radioactive glyceryl trinitrate (GTN) after preincubation with defined amounts of NO. The vascular content of GTN and the dinitrates (GDNs) 1,2-GDN and 1,3-GDN then was quantified. NO (3 microM, 30 min) significantly impaired bioactivation of GTN as indicated by a 30-50% reduction in the accumulation of 1,2-GDN and 1,3-GDN, whereas unchanged GTN was increased. Incubation with NO also reduced the stimulated specific activity of soluble guanylate cyclase isolated from human platelets. Its specific activity was reduced from 2.6 +/- 0.2 to 2.1 +/- 0.13 nmol of cGMP/mg/min. Relaxation studies with rings of porcine coronary arteries showed that NO-induced inhibition of vascular GTN metabolism and cGMP accumulation decreased the vasodilator potency of GTN by 10-fold. Further experiments showed that the duration of NO treatment is more important for this effect than the concentration of NO. We suggest that NO can inhibit vascular bioactivation of organic nitrates and might slightly desensitize soluble guanylate cyclase. The preferential venodilation induced by organic nitrates might be the result of the comparably low production of endogenous NO in veins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
547-54
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Nitric oxide inhibits vascular bioactivation of glyceryl trinitrate: a novel mechanism to explain preferential venodilation of organic nitrates.
pubmed:affiliation
Institut fur Pharmakologie, Medizinische Einrichtungen, Heinrich-Heine-Universitat, 40225 Dusseldorf, Germany. kojda@uni-duesseldorf.de
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't