Published online before print January 20, 2005, doi: 10.1161/01.RES.0000156275.06641.b2
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Submitted on August 20, 2004
Revised on January 5, 2005
Accepted on January 7, 2005
Increased PI3-Kinase in Presympathetic Brain Areas of the Spontaneously Hypertensive Rat
Shereeni J. Veerasingham ;
From the Department of Physiology and Functional Genomics (S.J.V., M.Y., M.K.R.), University of Florida, Gainesville; and the Departments of Physiology (K.H.B.) and Cell Biology (M.W.), University of Alabama, Birmingham.
* To whom correspondence should be addressed. E-mail: mraizada{at}phys.med.ufl.edu.
Existing evidence led us to hypothesize that increases in p85
, a regulatory subunit of PI3-kinase, in presympathetic brain areas contribute to hypertension. PI3-kinase p85, p110, and p110
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 p85/p110 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), p110 mRNA was 
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 p85 mRNA and PI3-kinase activity. Expression of a p85 dominant-negative mutant decreased norepinephrine (NE) transporter mRNA and [3H]NE uptake by 60% selectively in SHR neurons. In summary, increased p85/p110 expression in the PVN and RVLM is associated with increased PI3-kinase activity in the SHR. Furthermore, normalized PI3-kinase p85/p110 expression within the PVN might contribute to the overall effect of captopril, perhaps attributable to a consequent decrease in NE availability.
Key words: PI3-kinase • spontaneously hypertensive rats • norepinephrine transporter • paraventricular nucleus • rostral ventrolateral medulla
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