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(Stroke. 2002;33:1164.)
© 2002 American Heart Association, Inc.

Letters to the Editor

Re: Slowly Activating Potassium Conductance (I_D): A Potential Target for Stroke Therapy

Jean Michel Achard, MD, PhD

Physiology Department, CHU, Limoges, France

Oliver Godefroy, MD; Michel Andrejak, MD; Hakim Mazouz, MD Albert Fournier, MD

Departments of Neurology, Pharmacology, and Nephrology Internal Medicine, CHU, Amiens, France

Leonardo Fernandez, MD

Pathology Department, Yale Medical School, New Haven, Connecticut

To the Editor:

We read with great interest the article by Bains et al¹ in which they hypothesize that the blood pressure–independent susceptibility of spontaneous hypertensive rats (SHR) to stroke could be explained by increased angiotensin II levels in the brain nuclei. Indeed, they convincingly documented that resistance to death of magnocellular neurons of paraventricular nucleus (PVN) after injection of an N-methyl-D-aspartate receptor agonist (NMDAa) is present in normotensive rats but absent in SHR and that preadministration of saralasin into these nuclei of SHR generated resistance of these cells to NMDAa-induced death, by preventing the angiotensin II–mediated increase of neuronal excitability, which is secondary to inhibition of a D-type specific potassium conductance. Indeed, inhibition of this conductance results in higher frequency of depolarization in the penumbra surrounding a focal brain ischemia and, therefore, results in increased infarct size. However, while the authors stressed the potential pathophysiological significance of their observation by recalling that the AT1 receptor antagonist losartan protects SHR against stroke even at nonantihypertensive dose,² they unfortunately did not examine the effect of specific AT1 receptor blockade in their experimental model, and we wonder why they have chosen saralasin, a nonspecific angiotensin II antagonist.

Preadministration of losartan and candesartan have been shown to be more stroke protective than angiotensin-converting enzyme inhibitor (ACEI) in the gerbil model of acute brain ischemia by unilateral carotid ligation, whereas preadministration of ACEI with these AT1 receptor antagonists resulted in the same mortality as with ACEI alone, suggesting that stimulation of non–AT1 receptors was . . . [Full Text of this Article]

Alastair V. Ferguson, PhD

Department of Physiology, Queen’s University, Kingston, Ontario, Canada

Jaideep S. Bains, PhD

Neuroscience Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada