Abstract:
:Cyclosporine A (CsA)-induced hypertension appears to be caused in part by neurogenic vasoconstriction, but the mechanism by which CsA activates the sympathetic nervous system is unknown. In T lymphocytes, the cellular target of CsA and the macrolide immunosuppressant FK506 (as complexes with their endogenous cytoplasmic receptors, or immunophilins) is the Ca(2+)-calmodulin-dependent phosphatase calcineurin. The presence of calcineurin and its colocalization with immunophilin in the brain led us to hypothesize that the phosphatase also mediates CsA-induced sympathetic activation. We now report that sympathetic activity and arterial pressure in rats are increased not only by CsA but also by FK506, which is structurally unrelated to CsA but inhibits the same calcineurin-sensitive T-cell signaling pathway. In contrast, sympathetic activity and blood pressure are not increased by rapamycin, which forms an immunophilin complex that does not bind calcineurin. Furthermore, CsA- and FK506-induced sympathetic activation is attenuated for drug analogues possessing modest changes in molecular structure in a way that closely parallels the ability of each analogue to inhibit calcineurin-mediated T-cell signaling. These results implicate an important role for extralymphoid (ie, neuronal) calcineurin in mediating immunosuppressive drug toxicity.
journal_name
Circ Resjournal_title
Circulation researchauthors
Lyson T,Ermel LD,Belshaw PJ,Alberg DG,Schreiber SL,Victor RGdoi
10.1161/01.res.73.3.596subject
Has Abstractpub_date
1993-09-01 00:00:00pages
596-602issue
3eissn
0009-7330issn
1524-4571journal_volume
73pub_type
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pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.219279
更新日期:2010-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:2003-01-10 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.66.2.478
更新日期:1990-02-01 00:00:00
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更新日期:2014-05-09 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:2015-06-05 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.81.6.904
更新日期:1997-12-01 00:00:00
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更新日期:2008-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:1980-11-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.6.1482
更新日期:1992-12-01 00:00:00
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pub_type: 杂志文章,收录出版
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更新日期:2009-11-20 00:00:00
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pub_type: 杂志文章
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更新日期:1998-10-19 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1977-05-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.3.657
更新日期:1992-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.86.10.1093
更新日期:2000-05-26 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.2.315
更新日期:1988-02-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000237021.65103.24
更新日期:2006-08-04 00:00:00
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pub_type: 杂志文章
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更新日期:1992-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:2011-09-02 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.219089
更新日期:2010-10-15 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2014-01-03 00:00:00
abstract::Three models of altered autonomic innervation of the chick heart have been developed in the last few years. These include sympathetically aneural heart, parasympathetically aneural heart, and heart with cholinergic innervation reconstituted from the nodose placodes. The neural status of these hearts has been assessed ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.6.1547
更新日期:1989-12-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000107196.21335.2B
更新日期:2004-01-09 00:00:00
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pub_type: 杂志文章
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更新日期:2007-03-02 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1995-06-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.50.3.342
更新日期:1982-03-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.4.922
更新日期:1991-04-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:2008-05-09 00:00:00