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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1991-2-7
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pubmed:abstractText |
N alpha-benzoyl-L-arginine ethyl ester (BAEE) is a vasorelaxant which resembles an arginine-containing peptide; its action may be partially endothelium-dependent. Because L-arginine (ARG) has little potency as a vasorelaxant, it has been proposed that an arginine-containing peptide, rather than free ARG, is the immediate precursor of endothelium-derived relaxing factor/nitric oxide (EDRF/NO). In the present study we have characterized pharmacologically the vasorelaxant effect of BAEE and assessed the ability of BAEE to serve as a substrate for EDRF/NO synthesis. BAEE elicited a concentration-dependent vasorelaxation of guinea pig pulmonary artery (EC50 of 0.36 +/- 0.05 mM). This vasorelaxation was neither antagonized by -NG-methyl-L-arginine (100 microM), a competitive inhibitor of EDRF/NO synthesis from ARG, nor potentiated by superoxide dismutase (60 U/ml), a superoxide anion scavenger that prolongs EDRF lifetime. Additionally, compound LY 83583 (1 microM) and methylene blue (10 microM), inhibitors of soluble guanylyl cyclase, failed to block BAEE-induced vasorelaxation. Moreover, endothelium removal potentiated the vasorelaxant effect of BAEE 3-fold. Thus, BAEE-induced vasorelaxation is mediated by a direct action on vascular smooth muscle that is unrelated to EDRF/NO synthesis. Furthermore, ARG, but not BAEE, overcame the inhibition by NG-methyl-L-arginine of the acetylcholine-induced endothelium-dependent cyclic GMP accumulation in guinea pig aortic rings and of A23187-induced nitrite formation by cultured bovine aortic endothelial cells (nitrite is a convenient indicator of NO biosynthesis). Thus, BAEE cannot substitute for ARG as a substrate for EDRF/NO biosynthesis. Collectively, our findings support the notion that free ARG, rather than an arginine-containing peptide related to BAEE, is the immediate biosynthetic precursor of EDRF/NO.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcholine,
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrates,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/benzoylarginine ethyl ester,
http://linkedlifedata.com/resource/pubmed/chemical/omega-N-Methylarginine
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
255
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1348-53
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:2175803-Acetylcholine,
pubmed-meshheading:2175803-Animals,
pubmed-meshheading:2175803-Arginine,
pubmed-meshheading:2175803-Cyclic GMP,
pubmed-meshheading:2175803-Dose-Response Relationship, Drug,
pubmed-meshheading:2175803-Guinea Pigs,
pubmed-meshheading:2175803-Male,
pubmed-meshheading:2175803-Muscle, Smooth, Vascular,
pubmed-meshheading:2175803-Muscle Relaxation,
pubmed-meshheading:2175803-Nitrates,
pubmed-meshheading:2175803-Nitric Acid,
pubmed-meshheading:2175803-Nitric Oxide,
pubmed-meshheading:2175803-Norepinephrine,
pubmed-meshheading:2175803-Pulmonary Artery,
pubmed-meshheading:2175803-omega-N-Methylarginine
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pubmed:year |
1990
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pubmed:articleTitle |
L-arginine, but not N alpha-benzoyl-L-arginine ethyl ester, is a precursor of endothelium-derived relaxing factor.
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pubmed:affiliation |
Department of Pharmacology, Cornell University Medical College, New York, New York.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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