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Physiological Reviews, Vol. 81, No. 4, October 2001, pp. 1599-1658
Copyright ©2001 by the American Physiological Society
Department of Clinical Chemistry, Imperial College School of Medicine, Charing Cross Campus, London, United Kingdom
De Wardener, H. E.
The Hypothalamus and Hypertension. Physiol. Rev. 81: 1599-1658, 2001.
Most forms of
hypertension are associated with a wide variety of functional changes
in the hypothalamus. Alterations in the following substances are
discussed: catecholamines, acetylcholine, angiotensin II, natriuretic
peptides, vasopressin, nitric oxide, serotonin, GABA, ouabain,
neuropeptide Y, opioids, bradykinin, thyrotropin-releasing factor,
vasoactive intestinal polypeptide, tachykinins, histamine, and
corticotropin-releasing factor. Functional changes in these
substances occur throughout the hypothalamus but are particularly
prominent rostrally; most lead to an increase in sympathetic nervous
activity which is responsible for the rise in arterial pressure. A few
appear to be depressor compensatory changes. The majority of the
hypothalamic changes begin as the pressure rises and are particularly
prominent in the young rat; subsequently they tend to fluctuate and
overall to diminish with age. It is proposed that, with the possible
exception of the Dahl salt-sensitive rat, the hypothalamic changes
associated with hypertension are caused by renal and intrathoracic
cardiopulmonary afferent stimulation. Renal afferent stimulation occurs
as a result of renal ischemia and trauma as in the reduced renal mass
rat. It is suggested that afferents from the chest arise, at least in part, from the observed increase in left auricular pressure which, it
is submitted, is due to the associated documented impaired ability to
excrete sodium. It is proposed, therefore, that the hypothalamic
changes in hypertension are a link in an integrated compensatory
natriuretic response to the kidney's impaired ability to excrete sodium.
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