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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1997-3-19
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pubmed:abstractText |
In order to study the contribution of the nitric oxide (NO)-pathway to cholinergic vasodilatation in the resistance vessels of the human forearm, we infused acetylcholine (ACh; 0.1 1000 ng/kg/min) or methacholine (MCh; 0.1 A 100 ng/kg/min) in the presence of saline, the NO-scavenger and guanylate cyclase inhibitor methylene blue (MB; 1000 ng/kg/min), or the NO-synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 30 micrograms/kg/min) into the brachial artery of normotensive volunteers (n = 32), using venous occlusion plethysmography. We calculated the plasma concentrations of the infused compounds to obtain EC50-values (-log mol/l). ACh and MCh both caused concentration-dependent vasodilatation (EC50-values of 6.43 +/- 0.05 and 7.24 +/- 0.08, respectively). MB (13 mumol/l) did not change basal forearm blood flow (FBF) when administered alone, but it markedly potentiated the vasodilator response to ACh, shifting the concentration-response curve (CRC) leftwards by 1.5 log-step (p < 0.001). MB did not affect MCh-induced vasodilatation. L-NMMA (1 mmol/l) alone caused dose-dependent vasoconstriction that was subject to tachyphylaxis. In addition, L-NMMA caused a steepening of the slopes of the CRCs of ACh, and MCh L-NMMA attenuated the ACh-/MCh-induced vasodilator responses in the lowest concentration ranges (p < 0.05) only, but did not alter the response at higher concentrations. The 10-fold higher potency of MCh compared to ACh can be explained by the more rapid degradation of ACh by cholinesterases. The observation that high concentrations of L-NMMA only affect vasodilation mediated by low concentrations of ACh or MCh, suggests a second mechanism in cholinergic vasodilatation, such as a direct effect on smooth muscle cells or the release of a relaxing factor other than NO.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0803-7051
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
5
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
333-41
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8973750-Acetylcholine,
pubmed-meshheading:8973750-Adult,
pubmed-meshheading:8973750-Dose-Response Relationship, Drug,
pubmed-meshheading:8973750-Forearm,
pubmed-meshheading:8973750-Humans,
pubmed-meshheading:8973750-Male,
pubmed-meshheading:8973750-Methacholine Chloride,
pubmed-meshheading:8973750-Microcirculation,
pubmed-meshheading:8973750-Nitric Oxide,
pubmed-meshheading:8973750-Parasympathomimetics,
pubmed-meshheading:8973750-Vasodilation
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pubmed:year |
1996
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pubmed:articleTitle |
Comparison of cholinergic vasodilator responses to acetylcholine and methacholine in the human forearm.
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pubmed:affiliation |
Department of Nephrology, University Hospital Leiden, The Netherlands.
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pubmed:publicationType |
Journal Article,
Comparative Study
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