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Comparison of U46619‐, endothelin‐1‐ or phenylephrine‐induced changes in cellular Ca 2+ profiles and Ca 2+ sensitisation of constriction of pressurised rat resistance arteries
Author(s) -
Shaw Linda,
O'Neill Stephen,
Jones Carolyn J P,
Austin Clare,
Taggart Michael J
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705647
Subject(s) - vasomotion , phenylephrine , chemistry , tonic (physiology) , contraction (grammar) , vascular smooth muscle , medicine , endocrinology , anatomy , muscle contraction , biophysics , mesenteric arteries , vasodilation , smooth muscle , artery , biology , blood pressure
In pressurised rat mesenteric small arteries (50 mmHg), we examined the effects of stimulation with U46619, endothelin‐1 (ET‐1) or phenylephrine (PE) on changes in vessel diameter, global [Ca 2+ ] i , individual smooth muscle cell [Ca 2+ ] i and Ca 2+ ‐sensitisation of contraction. U46619 or ET‐1 gave tonic diameter reductions, whereas PE‐stimulated vessels gave tonic contractions or initial vasoconstrictions followed by diameter oscillations. Global [Ca 2+ ] i changes were transient for each agonist, with tonic constrictions being accompanied by maintained submaximal global [Ca 2+ ] i levels. U46619, ET‐1 or PE tonic constrictions were accompanied by apparently asynchronous [Ca 2+ ] i waves in individual smooth muscle cells of the vessel wall, as examined by confocal fluorescent microscopy. In vessels exhibiting vasomotion to PE, some apparent synchrony of activation of individual cells was evident; however, this was incomplete with many cells responding out of phase with their neighbours. In α ‐toxin‐permeabilised preparations, agonist‐induced Ca 2+ ‐sensitisation of constriction at submaximal Ca 2+ (pCa6.7) in the presence of GTP was greater with U46619 or ET than PE. We conclude that, in pressurised mesenteric arteries, (i) a general feature of receptor‐coupled constriction is the generation of periodic smooth muscle [Ca 2+ ] i waves; (ii) complete synchrony of Ca 2+ oscillations between smooth muscle cells is not a prerequisite for receptor‐coupled vasomotion; (iii) varied Ca 2+ ‐sensitising actions of agonists may partly determine tonic or phasic vessel responses to different stimuli.British Journal of Pharmacology (2004) 141 , 678–688. doi: 10.1038/sj.bjp.0705647