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Chronic inhibition of phosphoinositide‐3‐kinase (PI3K) in the nucleus of the solitary tract (NTS) of hypertensive rats increases blood pressure
Author(s) -
Zubcevic Jasenka,
Kasparov Sergey,
Raizada Mohan K,
Paton Julian F.R.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a899-c
Subject(s) - baroreflex , solitary tract , baroreceptor , blood pressure , solitary nucleus , mean arterial pressure , endocrinology , medicine , pi3k/akt/mtor pathway , heart rate , brainstem , biology , receptor , signal transduction , microbiology and biotechnology
The NTS is the site of termination of baroreceptor primary afferents and a major regulator of arterial pressure. Our previous work indicated an increase in PI3K signalling in brainstem/hypothalamic neuronal cultures from spontaneously hypertensive (SHRs) compared to normotensive Wistar Kyoto rats (WKYs; Yang & Raizada, 1999; Veerasingham et al. 2005). To investigate the functional implications of this, we chronically blocked PI3K activity in the NTS by overexpressing a dominant negative of the p85α regulatory subunit of PI3K (DNp85α) while measuring changes in mean arterial pressure (MAP) in both SHR and WKY conscious adult rats using radio telemetry. Transgene expression was confirmed immunohistochemically post hoc . In SHR, but not WKY, MAP increased from 146±3 to 169±9 mmHg three weeks post gene delivery (n=6; P<0.05) persisting over five weeks, with no change in the spontaneous baroreflex gain (sBRG) or heart rate (HR). There was no change in MAP, sBRG and HR in either WKYs or in the control animals expressing DNp85α and eGFP respectively. We conclude that in SHR, but not WKY, the endogenous PI3K signalling acts to regulate arterial pressure. NIH grant #HL33610.