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Role of phosphoinositide‐3‐kinase (PI3K) in the nucleus of the solitary tract (NTS) in the modulation of baroreceptor reflex function in the hypertensive rat
Author(s) -
Zubcevic Jasenka,
Polson Jaimie W,
Kasparov Sergey,
DiezFreire Carlos C,
Raizada Mohan K,
Paton Julian F.R.
Publication year - 2008
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.22.1_supplement.737.34
Subject(s) - baroreflex , baroreceptor , endocrinology , solitary nucleus , medicine , solitary tract , microinjection , angiotensin ii , losartan , blood pressure , heart rate , receptor
Previous in vitro studies indicate an angiotensin II (AngII)‐dependent increase in PI3K signaling in the brainstem neurones of the spontaneously hypertensive (SHRs) but not Wistar Kyoto rats (WKYs; Yang & Raizada, 1999; Veerasingham et al. 2005). Here, we chronically blocked PI3K activity in the NTS of SHR by lentiviral overexpression of a dominant negative form of the p85α regulatory subunit of PI3K (DNp85α). Perfusion pressure, heart rate, and activities of the phrenic nerve and lower thoracic sympathetic chain were measured in an in situ arterially perfused rat preparation. Baroreceptors were stimulated by increasing perfusion pressure by 30–50 mmHg before and after NTS microinjection of AngII. Transgene expression and sites of AngII injections were confirmed post hoc . PI3K blockade alone reduced both the cardiac (from −3.1±0.1 to −1.4±0.5 bpm/mmHg) and sympathetic (from −5.7±3.4 to −1.0±0.6 %baseline/mmHg) baroreflex components when compared to the control rats overexpressing GFP in the NTS. AngII (500 fmol) in the NTS reduced the gain of the cardiac baroreflex in both groups to a similar extent. In contrast, the AngII‐mediated depression of the sympathetic component of baroreflex seen in controls (by 65±17%) was abolished in the DNp85α group (15±57%). We conclude that in SHR, AngII via the PI3K signalling modulates the sympathetic but not the cardiac component of the baroreflex. NIH grant #HL33610.