| pubmed-article:12172218 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12172218 | lifeskim:mentions | umls-concept:C1123023 | lld:lifeskim |
| pubmed-article:12172218 | lifeskim:mentions | umls-concept:C0079281 | lld:lifeskim |
| pubmed-article:12172218 | lifeskim:mentions | umls-concept:C0028351 | lld:lifeskim |
| pubmed-article:12172218 | lifeskim:mentions | umls-concept:C0025962 | lld:lifeskim |
| pubmed-article:12172218 | lifeskim:mentions | umls-concept:C0003009 | lld:lifeskim |
| pubmed-article:12172218 | lifeskim:mentions | umls-concept:C0042396 | lld:lifeskim |
| pubmed-article:12172218 | lifeskim:mentions | umls-concept:C1333689 | lld:lifeskim |
| pubmed-article:12172218 | lifeskim:mentions | umls-concept:C0002085 | lld:lifeskim |
| pubmed-article:12172218 | lifeskim:mentions | umls-concept:C1742737 | lld:lifeskim |
| pubmed-article:12172218 | lifeskim:mentions | umls-concept:C2349975 | lld:lifeskim |
| pubmed-article:12172218 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:12172218 | pubmed:dateCreated | 2002-8-12 | lld:pubmed |
| pubmed-article:12172218 | pubmed:abstractText | Hypertension is associated with enhanced peripheral vascular resistance, which may be mediated by enhanced vasoconstriction. The impact of the recently detected G-protein beta3-subunit gene C825T polymorphism on the response to the major pressor mediators has been studied in vivo in the human microcirculation. We assessed the effects of endothelin-1 (ET-1), angiotensin II (AT), endothelin-antagonists (BQ-123 and BQ-788) and noradrenaline (NA, each 10-16-10-8 mol) on vasoconstriction in the human skin microcirculation in vivo in 25 healthy male volunteers (13 with CC genotype, 12 TC/TT genotype) using laser Doppler flowmetry. The effects of endothelium-derived vasodilation on NA-induced effects were studied using the NO-synthase inhibitor l-nitro-monomethyl-arginine (L-NMMA) and the alpha2-adrenoceptor-antagonist yohimbine (YO). ET-1, AT and NA caused a dose-dependent vasoconstriction (P < 0.001). In carriers of the 825T allele the response to ET-1, AT and NA was significantly enhanced leading to a shift to the left of the dose-response curve of up to two log units (ET-1: P < 0.001 vs. CC; AT: P < 0.01 vs. CC; NA: P < 0.05 vs. CC). After pretreatment with L-NMMA or YO, NA induced vasoconstriction was no longer different between subjects with the CC- and CT/TT genotypes. However, following combined pretreatment with both L-NMMA and YO, vasoconstriction to NA was significantly potentiated in carriers of the T-allele. Vasodilatation to an ETA-antagonist (BQ-123) was more pronounced in the CT/TT genotype, while ETB-antagonism (BQ-788) led to a more pronounced vasoconstriction in the CT/TT genotype (not significant vs. CC). Healthy, normotensive carriers of the 825T-allele have enhanced vasoconstriction to ET-1, AT and NA in the skin microcirculation. This enhanced vasoconstriction appears to be partially antagonized by an enhanced release of endothelium derived vasodilators mediated by the stimulation of endothelial alpha2-adrenoceptors. The GNB3 C825T polymorphism is potentially an attractive pharmacogenetic marker to predict hormone-mediated responses in humans. | lld:pubmed |
| pubmed-article:12172218 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:12172218 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12172218 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:12172218 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12172218 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:12172218 | pubmed:issn | 0960-314X | lld:pubmed |
| pubmed-article:12172218 | pubmed:author | pubmed-author:BruckHH | lld:pubmed |
| pubmed-article:12172218 | pubmed:author | pubmed-author:PhilippThomas... | lld:pubmed |
| pubmed-article:12172218 | pubmed:author | pubmed-author:SiffertWinfri... | lld:pubmed |
| pubmed-article:12172218 | pubmed:author | pubmed-author:WenzelRené... | lld:pubmed |
| pubmed-article:12172218 | pubmed:author | pubmed-author:SchäfersRafae... | lld:pubmed |
| pubmed-article:12172218 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12172218 | pubmed:volume | 12 | lld:pubmed |
| pubmed-article:12172218 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12172218 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12172218 | pubmed:pagination | 489-95 | lld:pubmed |
| pubmed-article:12172218 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:12172218 | pubmed:year | 2002 | lld:pubmed |
| pubmed-article:12172218 | pubmed:articleTitle | Enhanced vasoconstriction to endothelin-1, angiotensin II and noradrenaline in carriers of the GNB3 825T allele in the skin microcirculation. | lld:pubmed |
| pubmed-article:12172218 | pubmed:affiliation | Division of Nephrology & Hypertension, University Hospital, Essen, Germany. rene@rrwenzel.de | lld:pubmed |
| pubmed-article:12172218 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12172218 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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