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Med."],"abstract":"<jats:p>There is ample evidence supporting a role for angiotensin II type 2 receptor (AT<jats:sub>2<\/jats:sub>R) in counterbalancing the effects of angiotensin II (ang II) through the angiotensin II type 1 receptor by promoting vasodilation and having anti-inflammatory effects. Elastin insufficiency in both humans and mice results in large artery stiffness and systolic hypertension. Unexpectedly, mesenteric arteries from elastin insufficient (<jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>) mice were shown to have significant vasoconstriction to AT<jats:sub>2<\/jats:sub>R agonism <jats:italic>in vitro<\/jats:italic> suggesting that AT<jats:sub>2<\/jats:sub>R may have vasoconstrictor effects in elastin insufficiency. Given the potential promise for the use of AT<jats:sub>2<\/jats:sub>R agonists clinically, the goal of this study was to determine whether AT<jats:sub>2<\/jats:sub>R has vasoconstrictive effects in elastin insufficiency <jats:italic>in vivo<\/jats:italic>. To avoid off-target effects of agonists and antagonists, mice lacking AT<jats:sub>2<\/jats:sub>R (<jats:italic>Agtr2<\/jats:italic><jats:sup>\u2212\/<jats:italic>Y<\/jats:italic><\/jats:sup>) were bred to <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice and cardiovascular parameters were assessed in wild-type (WT), <jats:italic>Agtr2<\/jats:italic><jats:sup>\u2212\/<jats:italic>Y<\/jats:italic><\/jats:sup>, <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>, and <jats:italic>Agtr2<\/jats:italic><jats:sup>\u2212\/<jats:italic>Y<\/jats:italic><\/jats:sup><jats:italic>;Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> littermates. As previously published, <jats:italic>Agtr2<\/jats:italic><jats:sup>\u2212\/<jats:italic>Y<\/jats:italic><\/jats:sup> mice were normotensive at baseline and had no large artery stiffness, while <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice exhibited systolic hypertension and large artery stiffness. Loss of AT<jats:sub>2<\/jats:sub>R in <jats:italic>Eln<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice did not affect large artery stiffness or arterial structure but resulted in significant reduction of both systolic and diastolic blood pressure. These data support a potential vasocontractile role for AT<jats:sub>2<\/jats:sub>R in elastin insufficiency. Careful consideration and investigation are necessary to determine the patient population that might benefit from the use of AT<jats:sub>2<\/jats:sub>R agonists.<\/jats:p>","DOI":"10.3389\/fcvm.2021.782138","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T05:08:35Z","timestamp":1635743315000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Loss of Angiotensin II Type 2 Receptor Improves Blood Pressure in Elastin Insufficiency"],"prefix":"10.3389","volume":"8","author":[{"given":"Michelle","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn A.","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth A.","family":"Kozel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert 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