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(Hypertension. 2009;53:97.)
© 2009 American Heart Association, Inc.

Original Articles

Chronic Blockade of Phosphatidylinositol 3-Kinase in the Nucleus Tractus Solitarii Is Prohypertensive in the Spontaneously Hypertensive Rat

Jasenka Zubcevic; Hidefumi Waki; Carlos Diez-Freire; Alexandra Gampel; Mohan K. Raizada; Julian F.R. Paton

From the Department of Physiology and Pharmacology (J.Z., A.G., J.F.R.P.), Bristol Heart Institute, School of Medical Sciences, University of Bristol, Bristol, United Kingdom; Department of Physiology and Functional Genomics (C.D.-F., M.K.R.), University of Florida, Gainesville; and the Department of Physiology (H.W.), University of Wakayama, Wakayama, Japan. Current address (J.Z.): Department of Integrative Physiology, Health Science Center, University of North Texas, Ft Worth.

Correspondence to Julian F.R. Paton, Department of Physiology and Pharmacology, Bristol Heart Institute, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, United Kingdom. E-mail Julian.F.R.Paton{at}bris.ac.uk

Phosphatidylinositol 3-kinase (PI3K) within brain stem neurons has been implicated in hypertension in the spontaneously hypertensive rat (SHR). Previously, we demonstrated elevated expression of PI3K subunits in rostral ventrolateral medulla and paraventricular nucleus of SHRs compared with Wistar-Kyoto rats. Here, we considered expression levels of PI3K in the nucleus tractus solitarii, a pivotal region in reflex regulation of arterial pressure, and determined its functional role for arterial pressure homeostasis in SHRs and Wistar-Kyoto rats. We found elevated mRNA levels of p110β and p110 catalytic PI3K subunits in the nucleus tractus solitarii of adult (12 to 14 weeks old) SHRs relative to the age-matched Wistar-Kyoto rats (fold differences relative to β-actin: 1.7±0.2 versus 1.01±0.08 for p110β, n=6, P<0.05; 1.62±0.15 versus 1.02±0.1 for p110, n=6, P<0.05). After chronic blockade of PI3K signaling in the nucleus tractus solitarii by lentiviral-mediated expression of a mutant form of p85, systolic pressure increased from 175±3 mm Hg to 191±6 mm Hg (P<0.01) in SHRs but not in Wistar-Kyoto rats. In addition, heart rate increased (from 331±6 to 342±6 bpm; P<0.05) and spontaneous baroreflex gain decreased (from 0.7±0.07 to 0.5±0.04 ms/mm Hg; P<0.001) in the SHRs. Thus, PI3K signaling in the nucleus tractus solitarii of SHR restrains arterial pressure in this animal model of neurogenic hypertension.

Key Words: hypertension • brain stem • NTS • PI3K • baroreflex control