(Hypertension. 1999;34:1301.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
AT1 Receptors Mediate Excitatory Inputs to Rostral Ventrolateral Medulla Pressor Neurons From Hypothalamus
From the Department of Physiology and Institute for Biomedical Research, The University of Sydney, Sydney, New South Wales, Australia.
Correspondence to Dr R.A.L. Dampney, Department of Physiology, F13, University of Sydney, Sydney, NSW 2006, Australia. E-mail rogerd{at}physiol.usyd.edu.au
Abstract—Angiotensin
II type 1 (AT1) receptors are located on pressor neurons in
the rostral ventrolateral medulla, and their activation results in an
increase in arterial pressure. However, the normal role of
these AT1 receptors in cardiovascular
regulation is unknown. In this study, we tested the hypothesis that
these receptors mediate synaptic excitation of rostral ventrolateral
medullary pressor neurons in response to activation of the hypothalamic
paraventricular nucleus. In anesthetized rats,
microinjections of the 
-aminobutyric acid receptor
antagonist bicuculline were made into the
paraventricular nucleus; this injection causes activation
of the nucleus as a consequence of disinhibition. The pressor and
sympathoexcitatory responses evoked by
paraventricular nucleus activation were significantly
reduced (by 
40% to 50%) after microinjection of the specific
AT1 receptor antagonists losartan or
L-158,809 into the rostral ventrolateral medulla on the ipsilateral,
but not contralateral, side. These responses were reduced to a similar
degree after microinjections of the neuroinhibitory
compound muscimol into the ipsilateral, but not contralateral, rostral
ventrolateral medulla. However, bilateral microinjections of the
glutamate receptor antagonist kynurenic acid into the
rostral ventrolateral medulla had no effect on the responses evoked
from the paraventricular nucleus. Conversely, bilateral
microinjections of kynurenic acid into the rostral ventrolateral
medulla virtually abolished the
somatosympathoexcitatory reflex, whereas
bilateral microinjections of losartan or L-158,809 had no
effect on this reflex. The results indicate that excitatory synaptic
inputs to pressor neurons in the rostral ventrolateral medulla arising
from activation of the paraventricular nucleus are mediated
predominantly by AT1 receptors.
Key Words: angiotensin II • blood pressure • brain • receptors, glutamate • bicuculline • blood vessels
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