Published online before print January 22, 2008, doi: 10.1161/HYPERTENSIONAHA.107.106898
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(Hypertension. 2008;51:622.)
© 2008 American Heart Association, Inc.
Editorial Commentaries |
New Twist to the Role of the Renin-Angiotensin System in Heart Failure
Aldosterone Upregulates Renin-Angiotensin System Components in the Brain
From the Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research, and Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Correspondence to Ernesto L. Schiffrin, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Côte Ste-Catherine Rd, B-127, Montreal, Quebec, Canada H3T 1E2. E-mail ernesto.schiffrin@mcgill.ca
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The renin-angiotensin system has been shown to be upregulated in peripheral tissues, particularly the vasculature, in a number of different cardiovascular conditions. As well, many actions on the vasculature usually attributed to direct effects of angiotensin II (Ang II) are now known to be mediated at least in part by aldosterone.1,2 In the present issue, Yu et al3 demonstrate that components of the renin-angiotensin system (RAS) are upregulated in the brain in a model of ischemic heart failure in rats. They demonstrate that aldosterone is elevated in heart failure in the brain proportionately to the increase in the circulation. This increase results in mineralocorticoid receptor–mediated stimulation of hypothalamic angiotensin I-converting enzyme (ACE) and angiotensin type 1 (AT1) receptor mRNA and protein, enhanced reduced nicotinamide-adenine dinucleotide phosphate oxidase activity, and reactive oxygen species in the paraventricular nucleus. Activation of the renin-angiotensin system and its mediators leads to increased neuronal activity and sympathetic drive and elevated circulating levels of plasma norepinephrine. All of these effects were blocked in this model by intracerebroventricular administration of a mineralocorticoid receptor antagonist. They suggest that, whereas penetration of aldosterone into the brain correlates with plasma levels but may be variable for ACE inhibitors, AT1, and mineralocorticoid receptor blockers, adequate inhibition of these central effects with these RAS blockers may not be achieved without inducing important adverse effects. Thus, inhibition of aldosterone synthesis or release may be a better approach to reduce these actions of aldosterone on the brain that participate in the pathophysiology of
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Hypertension 2008 51: 727-733.
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