Linked Life Data

17242303

Source:http://linkedlifedata.com/resource/pubmed/id/17242303

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-2-16
pubmed:abstractText
l-arginine is the substrate used by NO synthase to produce the vasodilator NO. However, in several human diseases, such as hyperhomocysteinemia, diabetes mellitus, and hypertension, there is an increase in serum levels of methylated l-arginines, such as asymmetrical dimethylarginine (ADMA), which cannot be used by NO synthase to produce NO. Yet, the functional consequence of increased levels of ADMA on the vasomotor function of resistance vessels has not been delineated. We hypothesized that elevated levels of exogenous ADMA inhibit NO mediation of flow/shear stress-dependent dilation of isolated arterioles. In the presence of indomethacin, isolated arterioles from rat gracilis muscle (approximately 165 microm at 80 mm Hg) were incubated with ADMA (10(-4) mol/L), which eliminated the dilations to increases in intraluminal flow (control: from 164+/-5.4 to 188+/-3.8 microm versus ADMA: from 171+/-6.1 to 173+/-6.3 microm at 20 microL/min). ADMA did not affect dilations to nifedipine (10(-6) mol/L; control: 63.4+/-2%, ADMA: 65.8+/-3%) or 8-bromo cGMP (10(-4) mol/L; control: 51.2+/-2.1%, ADMA: 49.3+/-3.4%). In addition, ADMA elicited significant constriction of arterioles (from 173+/-17 microm to 138+/-16 microm at 80 mm Hg), which was prevented by previous incubation of arterioles with polyethylene-glycol (PEG) superoxide dismutase (SOD; 120 U/mL, control: 155+/-11 microm versus ADMA: 150+/-14 microm). Correspondingly, ADMA increased PEG-SOD reversible manner the production of vascular superoxide assessed by lucigenin-enhanced chemiluminescence and ethidium bromide fluorescence. Thus, increased levels of ADMA in various diseases could inhibit the regulation of arteriolar resistance by shear stress-induced release of NO and elicit superoxide-mediated increase in basal tone, both of which favor the development of hypertension.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
563-8
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Asymmetrical dimethylarginine inhibits shear stress-induced nitric oxide release and dilation and elicits superoxide-mediated increase in arteriolar tone.
pubmed:affiliation
Department of Pathophysiology, Semmelweis University, Budapest, Hungary.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural