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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-3-3
pubmed:abstractText
We tested the hypothesis that the endogenous nitric oxide synthetase (NOS) inhibitor, asymmetric dimethylarginine (ADMA), regulates cardiovascular function by central mechanisms. In in vivo studies, rats received intracerebroventricular (i.c.v.) injection of isotonic saline, ADMA (1 mg), l-arginine (3 mg), and N omega-nitro-l-arginine methylester (l-NAME, 1 mg). Baroreflex function was then assessed by intravenous (i.v.) injection of phenylephrine. Central application of exogenous NOS inhibitor, l-NAME, increased mean arterial blood pressure and decreased heart rate. However, application of the endogenous NOS inhibitor, ADMA, decreased mean arterial blood pressure and heart rate simultaneously (-39 +/- 6 mm Hg and -50 +/- 8 beats/min, respectively). Both l-NAME (i.c.v.) and ADMA (i.c.v.) significantly inhibited the baroreflex function, indicating a regulatory role of central nitric oxide in controlling baroreflex function. In contrast to the central effect, intravenous injection of ADMA caused dose-dependent increases in mean arterial blood pressure that could be blocked by l-NAME pretreatment. In vitro studies using aortic rings demonstrated that ADMA (10(-4)M) significantly increased the concentration of acetylcholine for the threshold response (EC15) and half-maximal response (EC50). This indicates that ADMA inhibits the constitutive isoform of NOS in the endothelium. ADMA may have functional importance in regulating cardiovascular function by mechanisms in addition to the inhibition of nitric oxide synthesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0160-2446
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
439-46
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Central and peripheral effects of asymmetric dimethylarginine, an endogenous nitric oxide synthetase inhibitor.
pubmed:affiliation
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622, USA.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, Non-U.S. Gov't