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(Hypertension. 2008;52:621.)
© 2008 American Heart Association, Inc.

Editorial Commentaries

Brain Angiotensin and Heart Failure

Further Evidence for a Critical Role of Mitogen-Activated Protein Kinases

Roger A.L. Dampney

From the Bosch Institute and School of Medical Sciences (Physiology), University of Sydney, Australia.

Correspondence to Dr R.A.L. Dampney, Bosch Institute and School of Medical Sciences (Physiology), University of Sydney, NSW 2006, Australia. E-mail rogerd@physiol.usyd.edu.au

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In both humans and animals, heart failure is associated with sympathoexcitation and increased activity of the renin–angiotensin system.^1,2 Studies in animals have shown that in heart failure, there is increased expression of angiotensin type 1 (AT₁) receptors in key brain regions regulating sympathetic activity, such as the nucleus of the solitary tract, rostral ventrolateral medulla (RVLM), and the hypothalamic paraventricular nucleus (PVN),² as well as in the area postrema and subfornical organ (SFO), both of which are circumventricular organs that are accessible to circulating angiotensin II (Ang II). It has long been known that Ang II in the RVLM, PVN, and SFO can increase blood pressure and sympathetic activity,^2,3 and there is good evidence in rats and rabbits that upregulation of the brain renin-angiotensin system contributes to increased sympathetic activity.^2,4

The mechanism by which increased expression of AT₁ receptors occurs in heart failure has been the subject of much recent attention. It is known that Ang II can upregulate its own receptor,⁵ and a recent study by Chan et al⁶ showed that in the RVLM, Ang II triggers via AT₁ receptors increased intracellular production of superoxide and phosphorylation of the mitogen-activated protein kinase (MAPK) extracellular signal-regulated protein kinase, which is also known as p44/42 MAPK. Furthermore, microinjection into the RVLM of an antisense oligonucleotide that suppressed p44/42 activation also significantly reduced the pressor effect as well as increased AT₁ receptor expression in the RVLM induced by a 1-week ICV infusion of Ang II.⁶ Thus, these observations indicate that in . . . [Full Text of this Article]

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Mitogen-Activated Protein Kinases Mediate Upregulation of Hypothalamic Angiotensin II Type 1 Receptors in Heart Failure Rats

Shun-Guang Wei, Yang Yu, Zhi-Hua Zhang, Robert M. Weiss, and Robert B. Felder
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