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However, it is unknown whether stiffer large arteries affect cerebral and skeletal muscle feed artery responses to vasoconstrictors.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>In a mouse model with greater large artery stiffness (<jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>), we find an exacerbated vasoconstrictor response to angiotensin\u00a0II in cerebral arteries, but not skeletal muscle feed arteries, thus implicating altered cerebral artery angiotensin\u00a0II responsiveness in the poor brain outcomes associated with greater large artery stiffness.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Greater stiffness of the large elastic arteries is associated with end\u2010organ damage and dysfunction. At the same time, resistance artery vasoconstrictor responsiveness influences vascular tone and organ blood flow. However, it is unknown whether large elastic artery stiffness modulates the responsiveness to vasoconstrictors in resistance arteries of the cerebral or skeletal muscle circulations. We previously described the elastin haploinsufficient (<jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>) mouse as a model with greater aortic stiffness, but with similar cerebral and skeletal muscle feed artery stiffness to wild\u2010type (<jats:italic>Eln<\/jats:italic><jats:sup>+\/+<\/jats:sup>) mice. Here, we used this model to examine the relationship between large elastic artery stiffness and resistance artery vasoconstrictor responses. In middle cerebral arteries (MCAs), vasoconstriction in response to angiotensin\u00a0II (Ang\u00a0II) was \u223c40% greater in <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> compared with <jats:italic>Eln<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.02), and this group difference was ameliorated by losartan, indicating a role for Ang\u00a0II type\u00a01 receptors (AT1Rs). In gastrocnemius feed arteries, <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> and <jats:italic>Eln<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice did not differ in the response to Ang\u00a0II. In addition, the vasoconstrictor responses to noradrenaline, endothelin\u20101 and potassium chloride were not different between <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> and <jats:italic>Eln<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice for either MCAs or gastrocnemius feed arteries. The MCA AT1R gene expression did not differ between groups, whereas Ang\u00a0II type\u00a02 receptor gene expression was \u223c50% lower in MCAs from <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> <jats:italic>versus Eln<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.01). In conclusion, greater large elastic artery stiffness is associated with an exacerbated vasoconstriction response to Ang\u00a0II in cerebral arteries, but is not associated with the responses to other vasoconstrictors in either cerebral or skeletal muscle feed arteries.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep087453","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T14:22:00Z","timestamp":1547216520000},"page":"434-442","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cerebral and skeletal muscle feed artery vasoconstrictor responses in a mouse model with greater large elastic artery stiffness"],"prefix":"10.1113","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1612-4545","authenticated-orcid":false,"given":"Ashley E.","family":"Walker","sequence":"first","affiliation":[{"name":"Department of Human Physiology University of Oregon  Eugene OR 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