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) All Versions of this Article: 293/1/H152    most recent 00268.2006v1 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 (2) Citing Articles via Google Scholar Google Scholar Articles by Zhang, D. X. Articles by Campbell, W. B. Search for Related Content PubMed PubMed Citation Articles by Zhang, D. X. Articles by Campbell, W. B.

ACh-induced relaxations of rabbit small mesenteric arteries: role of arachidonic acid metabolites and K⁺

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin

Submitted 15 March 2006 ; accepted in final form 24 February 2007

ACh-induced endothelium-dependent relaxation in rabbit small mesenteric arteries is resistant to N-nitro-L-arginine (L-NA) and indomethacin but sensitive to high K⁺, indicating the relaxations are mediated by endothelium-derived hyperpolarizing factors (EDHFs). The identity of the EDHFs in this vascular bed remains undefined. Small mesenteric arteries pretreated with L-NA and indomethacin were contracted with phenylephrine. ACh (10^–10 to 10^–6 M) caused concentration-dependent relaxations that were shifted to the right by lipoxygenase inhibition and the Ca²⁺-activated K⁺ channel inhibitors apamin (100 nM) or charybdotoxin (100 nM) and eliminated by the combination of apamin plus charybdotoxin. Relaxations to ACh were also blocked by a combination of barium (200 µM) and apamin but not barium plus charybdotoxin. Addition of K⁺ (10.9 mM final concentration) to the preconstricted arteries elicited small relaxations. K⁺ addition before ACh restored the charybdotoxin-sensitive component of relaxations to ACh. K⁺ (10.9 mM) also relaxed endothelium-denuded arteries, and the relaxations were inhibited by barium but not by charybdotoxin and apamin. With the use of whole cell patch-clamp analysis, ACh (10^–7 M) stimulated voltage-dependent outward K⁺ current from endothelial cells, which was inhibited by charybdotoxin, indicating K⁺ efflux. Arachidonic acid (10^–7 to 10^–4 M) induced concentration-related relaxations that were inhibited by apamin but not by charybdotoxin and barium. Addition of arachidonic acid after K⁺ (10.9 mM) resulted in more potent relaxations to arachidonic acid compared with control without K⁺ (5.9 mM). These findings suggest that, in rabbit mesenteric arteries, ACh-induced, L-NA- and indomethacin-resistant relaxation is mediated by endothelial cell K⁺ efflux and arachidonic acid metabolites, and a synergism exists between these two separate mechanisms.

acetylcholine; potassium channels; lipoxygenase; endothelium-derived hyperpolarizing factor

This article has been cited by other articles:

				K. M. Gauthier, Y. Chawengsub, D. H. Goldman, R. E. Conrow, S. Anjaiah, J. R. Falck, and W. B. Campbell 11(R),12(S),15(S)-trihydroxyeicosa-5(Z),8(Z),13(E)-trienoic acid: an endothelium-derived 15-lipoxygenase metabolite that relaxes rabbit aorta Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1467 - H1472. [Abstract] [Full Text] [PDF]

				N. T. Aggarwal, Y. Chawengsub, K. M. Gauthier, H. Viita, S. Yla-Herttuala, and W. B. Campbell Endothelial 15-Lipoxygenase-1 Overexpression Increases Acetylcholine-Induced Hypotension and Vasorelaxation in Rabbits Hypertension, February 1, 2008; 51(2): 246 - 251. [Abstract] [Full Text] [PDF]