Comparison of U46619‐, endothelin‐1‐ or phenylephrine‐induced changes in cellular Ca2+ profiles and Ca2+ sensitisation of constriction of pressurised rat resistance arteries

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Abstract
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 [Ca2+]i, individual smooth muscle cell [Ca2+]i and Ca2+‐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 [Ca2+]i changes were transient for each agonist, with tonic constrictions being accompanied by maintained submaximal global [Ca2+]i levels. U46619, ET‐1 or PE tonic constrictions were accompanied by apparently asynchronous [Ca2+]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 Ca2+‐sensitisation of constriction at submaximal Ca2+ (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 [Ca2+]i waves; (ii) complete synchrony of Ca2+ oscillations between smooth muscle cells is not a prerequisite for receptor‐coupled vasomotion; (iii) varied Ca2+‐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

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