HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Ross, J. Articles by Armstead, W. M. Search for Related Content PubMed PubMed Citation Articles by Ross, J. Articles by Armstead, W. M.

LOCAL CONTROL OF CIRCULATION

Differential role of PTK and ERK MAPK in superoxide impairment of K_ATP and K_Ca channel cerebrovasodilation

Departments of Anesthesia and Pharmacology, University of Pennsylvania, Philadelphia, PA 19104

Submitted 6 January 2003 ; accepted in final form 24 March 2003

Previously, superoxide (O₂ ^-) has been observed to impair pial artery dilation (PAD) to activators of the ATP-sensitive (K_ATP) and calcium-sensitive (K_Ca) K⁺ channels. This study tested the hypothesis that activation of protein tyrosine kinase (PTK) and the ERK isoform of MAPK by O₂ ^- contribute to impairment of K_ATP and K_Ca channel PAD. Exposure of the cerebral cortex to a xanthine oxidase O₂ ^--generating system (OX) blunted PAD to cromakalim, a K_ATP agonist, but preadministration of genistein, a PTK antagonist, or U-0126, an ERK MAPK inhibitor, almost completely prevented such impairment (11 ± 1 and 22 ± 1 vs. 3 ± 1 and 7 ± 1 vs. 10 ± 1 and 16 ± 2% for cromakalim with 10^-8 and 10^-6 M PAD during control, OX, and OX + genistein conditions). In contrast, neither genistein nor U-0126 robustly protected PAD to NS-1619, a K_Ca agonist, after OX exposure (11 ± 1 and 18 ± 2 vs. 1 ± 1 and 2 ± 1 vs. 4 ± 1 and 6 ± 1% for 10^-8 and 10^-6 M NS-1619 during control, OX, and OX + genistein conditions). These data show that PTK and ERK MAPK activation contribute to O₂ ^--induced K_ATP and K_Ca channel PAD impairment and suggest a differential greater role for PTK and ERK MAPK in K_ATP vs. K_Ca channel PAD impairment.

oxygen free radicals; K⁺ channels; signal transduction

This article has been cited by other articles:

				H. Xu, X. Bian, S. W. Watts, and A. Hlavacova Activation of Vascular BK Channel by Tempol in DOCA-Salt Hypertensive Rats Hypertension, November 1, 2005; 46(5): 1154 - 1162. [Abstract] [Full Text] [PDF]

				D. D. Gutterman, H. Miura, and Y. Liu Redox Modulation of Vascular Tone: Focus of Potassium Channel Mechanisms of Dilation Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): 671 - 678. [Abstract] [Full Text] [PDF]