Abstract:
:Existing evidence led us to hypothesize that increases in p85alpha, a regulatory subunit of PI3-kinase, in presympathetic brain areas contribute to hypertension. PI3-kinase p85alpha, p110alpha, and p110delta mRNA was 1.5- to 2-fold higher in the paraventricular nucleus (PVN) of spontaneously hypertensive rats (SHR) compared with their controls, Wistar Kyoto rats (WKY). The increase in p85alpha/p110delta was attenuated in SHR treated with captopril, an angiotensin (Ang)-converting enzyme inhibitor, from in utero to 6 months of age. In the rostral ventrolateral medulla (RVLM), p110delta mRNA was approximately 2-fold higher in SHR than in WKY. Moreover, the increases in mRNA were associated with higher PI3-kinase activity in both nuclei. The functional relevance was studied in neuronal cultures because SHR neurons reflect the augmented p85alpha mRNA and PI3-kinase activity. Expression of a p85 dominant-negative mutant decreased norepinephrine (NE) transporter mRNA and [3H]NE uptake by approximately 60% selectively in SHR neurons. In summary, increased p85alpha/p110delta expression in the PVN and RVLM is associated with increased PI3-kinase activity in the SHR. Furthermore, normalized PI3-kinase p85alpha/p110delta expression within the PVN might contribute to the overall effect of captopril, perhaps attributable to a consequent decrease in NE availability.
journal_name
Circ Resjournal_title
Circulation researchauthors
Veerasingham SJ,Yamazato M,Berecek KH,Wyss JM,Raizada MKdoi
10.1161/01.RES.0000156275.06641.b2subject
Has Abstractpub_date
2005-02-18 00:00:00pages
277-9issue
3eissn
0009-7330issn
1524-4571pii
01.RES.0000156275.06641.b2journal_volume
96pub_type
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更新日期:2005-02-04 00:00:00
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更新日期:2013-09-13 00:00:00
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更新日期:2009-09-11 00:00:00
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更新日期:1998-09-21 00:00:00
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pub_type: 杂志文章
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更新日期:1992-12-01 00:00:00
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