ACh-induced relaxations of rabbit small mesenteric arteries: role of arachidonic acid metabolites and K+. Am J Physiol Heart Circ Physiol 2007 Jul;293(1):H152-9
Date
03/06/2007Pubmed ID
17337603DOI
10.1152/ajpheart.00268.2006Scopus ID
2-s2.0-34547112024 (requires institutional sign-in at Scopus site) 29 CitationsAbstract
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 Ca(2+)-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 microM) 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.
Author List
Zhang DX, Gauthier KM, Chawengsub Y, Campbell WBAuthors
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinDavid X. Zhang MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AcetylcholineAnimals
Arachidonic Acid
Dose-Response Relationship, Drug
In Vitro Techniques
Male
Mesenteric Arteries
Potassium
Potassium Channel Blockers
Potassium Channels
Rabbits
Vasodilation
