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(Hypertension. 2006;47:1054.)
© 2006 American Heart Association, Inc.

Original Articles

Expression of Constitutively Active Angiotensin Receptors in the Rostral Ventrolateral Medulla Increases Blood Pressure

Andrew M. Allen; Jaspreet K. Dosanjh; Marco Erac; Sashikala Dassanayake; Ross D. Hannan; Walter G. Thomas

From the Department of Physiology (A.M.A., J.K.D., M.E., S.D.) and Howard Florey Institute (A.M.A.), University of Melbourne; The Peter MacCallum Cancer Research Institute (R.D.H.); and the Baker Heart Research Institute (W.G.T.), Melbourne, Victoria, Australia.

Correspondence to Andrew M. Allen, PhD, Dept of Physiology, University of Melbourne, Vic, 3010, Australia. E-mail a.allen{at}unimelb.edu.au

Angiotensin type 1A (AT_1A) receptors are expressed within the rostral ventrolateral medulla, and microinjections of angiotensin II into this region increase sympathetic vasomotor tone. To determine the effect of sustained increases in AT_1A receptor density or activity in rostral ventrolateral medulla, we used radiotelemetry to monitor blood pressure in conscious rats before and after bilateral microinjection into the rostral ventrolateral medulla of adenoviruses encoding the wild-type AT_1A receptor or a constitutively active version of the receptor (Asn¹¹¹Gly, [N111G]AT_1A). The constitutively active receptor signals in the absence of angiotensin II. Adenovirus-directed receptor expression was extensively characterized both in vitro and in vivo. We established that adenoviral infection was limited to the rostral ventrolateral medulla and that receptor expression was sustained for 10 days; we also observed that adenoviral transgene expression occurs in glia, with no transgene expression observed in neurons of the rostral ventrolateral medulla. Rats receiving the wild-type AT_1A receptor showed no change in blood pressure, whereas animals receiving the [N111G]AT_1A receptor displayed an increase in blood pressure that persisted for 3 to 4 days before returning to basal levels. These data indicate that increased AT_1A receptor activity (not just overexpression) is a primary determinant of efferent drive from rostral ventrolateral medulla and reveal counterregulatory processes that moderate AT_1A receptor actions at this crucial relay point. More importantly, they imply that constitutive receptor signaling in glia of the rostral ventrolateral medulla can modulate the activity of adjacent neurons to change blood pressure.

Key Words: receptor, angiotensin • rats, inbred WKY • blood pressure

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