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(Circulation Research. 2005;97:201.)
© 2005 American Heart Association, Inc.

Editorials

Targeting Arterial Chemoreceptor Over-Activity in Heart Failure With a Gas

David J. Paterson

From the University Laboratory of Physiology, Oxford, UK.

Correspondence to David Paterson, University Laboratory of Physiology, Parks Rd, Oxford OX1 3PT, UK. E-mail david.paterson@physiol.ox.ac.uk

See related article, pages 260–267

Key Words: carotid body • nitric oxide • gene transfer • heart failure

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

With an aging population the prevalence of heart failure (HF) continues to rise. In the United States almost 5 million people experience HF, often with a poor prognosis resulting in 20% of patients dying within 1 year and 80% mortality within 8 years.¹ Although the mechanisms underpinning cardiac failure are not firmly established, several converging events ranging from depressed contractility itself,² diastolic dysfunction,³ failing energy stores,⁴ abnormal cell growth,³ and defective beta adrenergic signaling⁵ are implicated. Neurohumoral activation also appears to play a significant role in amplifying harmful substrate to trigger lethal ventricular arrhythmia which may account for 50% of all deaths that are sudden and unexpected.⁶ The precise role of abnormal neurohumoral signaling is still unclear but is thought to involve a synergistic activation of the sympathetic nervous system with the renin-angiotensin-aldosterone system^7,8 and diminished parasympathetic activity.⁹ Emerging evidence now suggests that an aspect of impaired neurohumoral signaling in HF may arise from dysregulation of the arterial chemoreflex at the level of the carotid bodies by oxygen-free radicals.

Stimulation of the carotid body (CB) arterial chemoreceptors provides an excitatory input to activate the sympathetic nervous system.¹⁰ Chronic HF causes a sustained activation of the sympathetic nervous system¹¹ and is also associated with enhanced chemosensitivity in both clinical and experimental HF.^12,13 The type I (glomus) cell of the CB is thought to be the primary chemoreceptor sensor. There is an extensive plexus of nitric oxide synthase (predominately nNOS) positive immunoreactivity and NADPH-diaphorase activity in the intrinsic neurons that innervate intraglomic . . . [Full Text of this Article]