Source:http://linkedlifedata.com/resource/pubmed/id/12438540
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| lifeskim:mentions | |
| pubmed:dateCreated |
2002-11-19
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| pubmed:abstractText |
Numerous studies support the concept that centrally acting antihypertensive drugs, such as imidazolines, mediate sympathoinhibition not only via activation of central nervous alpha2-adrenoceptors (alpha2-AR) but also via imidazoline-1 receptors (I1-R). An additional presynaptic involvement in sympathetic neurotransmission of imidazolines, via I1-R independent of alpha2-AR, is still controversial and remains to be clarified in the heart. Concentration response curves on endogenous norepinephrine (NE) overflow evoked by stimulation of epicardial postganglionic sympathetic nerves in isolated buffer-perfused rat hearts were performed for brimonidine, moxonidine, rauwolscine, 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane (AGN192403), and efaroxan. To unmask an I1-R-mediated effect of moxonidine, hearts were pre-exposed in additional experiments with brimonidine or rauwolscine with or without AGN192403 or efaroxan, respectively. Moxonidine reduced stimulated NE overflow (log EC50: -6.15 +/- 0.14). AGN192403, a selective ligand at I1-R, had no influence on the dose-response curve of moxonidine (log EC50: -6.01 +/- 0.25). After pre-exposure to brimonidine [ stimulation 1 (S1) + stimulation 2 (S2); 10(-5) M], the inhibitory action of moxonidine was potentiated compared with control (32.0 +/- 2.8 versus 73.13 +/- 3.0%) and completely abolished with AGN192403 or efaroxan. This effect was also totally inhibited by pre-exposure with indomethacin (10(-7) M) and tricyclodecan-9-yl-xanthogenate (D-609), an inhibitor of phosphatidylcholine-selective phospholipase C (PC-PLC; 10(-7) M). Conversely, moxonidine was without modulating efficacy under alpha2-AR-blockade by rauwolscine. In summary, we demonstrate that moxonidine reduces NE release independently of I1-R, demonstrating the prominent effect of alpha2-AR in cardiac tissue under basal conditions. We also demonstrate that I1-R are involved in NE release under conditions of alpha2-AR-stimulation involving both a pathway of prostaglandins and PC-PLC.
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| pubmed:language |
eng
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| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic alpha-2 Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Bridged Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Buffers,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoline Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Indomethacin,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Quinoxalines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, alpha-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Drug,
http://linkedlifedata.com/resource/pubmed/chemical/Thiones,
http://linkedlifedata.com/resource/pubmed/chemical/Yohimbine,
http://linkedlifedata.com/resource/pubmed/chemical/brimonidine,
http://linkedlifedata.com/resource/pubmed/chemical/imidazoline I1 receptors,
http://linkedlifedata.com/resource/pubmed/chemical/moxonidine,
http://linkedlifedata.com/resource/pubmed/chemical/tricyclodecane-9-yl-xanthogenate
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| pubmed:status |
MEDLINE
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| pubmed:author | |
| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1163-70
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| pubmed:dateRevised |
2010-11-18
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| pubmed:articleTitle |
Presynaptic effects of moxonidine in isolated buffer perfused rat hearts: role of imidazoline-1 receptors and alpha2-adrenoceptors.
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| pubmed:affiliation |
Medizinische Klinik II, Medizinische Universität zu Lübeck, Lübeck, Germany. urschaefer@hotmail.com
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