{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T08:04:42Z","timestamp":1788595482853,"version":"build-2803163510"},"reference-count":71,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2015,6,15]]},"abstract":"\n Background<\/jats:title>\n \n Multifunctional calcium\/calmodulin\u2010dependent kinase\n II<\/jats:styled-content>\n (Ca\n MKII<\/jats:styled-content>\n ) is activated by angiotensin\n II<\/jats:styled-content>\n (Ang\n II<\/jats:styled-content>\n ) in cultured vascular smooth muscle cells (\n VSMCs<\/jats:styled-content>\n ), but its function in experimental hypertension has not been explored. The aim of this study was to determine the impact of Ca\n MKII<\/jats:styled-content>\n inhibition selectively in\n VSMCs<\/jats:styled-content>\n on Ang II hypertension.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Transgenic expression of a Ca\n MKII<\/jats:styled-content>\n peptide inhibitor in\n VSMCs<\/jats:styled-content>\n (\n TG SM<\/jats:styled-content>\n \u2010Ca\n MKIIN model<\/jats:styled-content>\n ) reduced the blood pressure response to chronic Ang\n II<\/jats:styled-content>\n infusion. The aortic depressor nerve activity was reset in hypertensive versus normotensive wild\u2010type animals but not in\n TG SM<\/jats:styled-content>\n \u2010Ca\n MKIIN<\/jats:styled-content>\n mice, suggesting that changes in baroreceptor activity account for the blood pressure difference between genotypes. Accordingly, aortic pulse wave velocity, a measure of arterial wall stiffness and a determinant of baroreceptor activity, increased in hypertensive versus normotensive wild\u2010type animals but did not change in\n TG SM<\/jats:styled-content>\n \u2010Ca\n MKIIN<\/jats:styled-content>\n mice. Moreover, examination of blood pressure and heart rate under ganglionic blockade revealed that\n VSMC<\/jats:styled-content>\n Ca\n MKII<\/jats:styled-content>\n inhibition abolished the augmented efferent sympathetic outflow and renal and splanchnic nerve activity in Ang II hypertension. Consequently, we hypothesized that\n VSMC<\/jats:styled-content>\n Ca\n MKII<\/jats:styled-content>\n controls baroreceptor activity by modifying arterial wall remodeling in Ang\n II<\/jats:styled-content>\n hypertension. Gene expression analysis in aortas from normotensive and Ang\n II<\/jats:styled-content>\n \u2013infused mice revealed that\n TG SM<\/jats:styled-content>\n \u2010Ca\n MKIIN<\/jats:styled-content>\n aortas were protected from Ang\n II<\/jats:styled-content>\n \u2013induced upregulation of genes that control extracellular matrix production, including collagen.\n VSMC<\/jats:styled-content>\n Ca\n MKII<\/jats:styled-content>\n inhibition also strongly altered the expression of muscle contractile genes under Ang\n II<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n CaMKII in\n VSMCs<\/jats:styled-content>\n regulates blood pressure under Ang\n II<\/jats:styled-content>\n hypertension by controlling structural gene expression, wall stiffness, and baroreceptor activity.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.115.001949","type":"journal-article","created":{"date-parts":[[2015,6,16]],"date-time":"2015-06-16T02:50:54Z","timestamp":1434423054000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Calcium\/Calmodulin\u2010Dependent Kinase II Inhibition in Smooth Muscle Reduces Angiotensin II\u2013Induced Hypertension by Controlling Aortic Remodeling and Baroreceptor Function"],"prefix":"10.1161","volume":"4","author":[{"given":"Anand M.","family":"Prasad","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald A.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel 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