{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:32:03Z","timestamp":1792042323925,"version":"4.4.0"},"reference-count":43,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:p> Overstimulation of the renin-angiotensin system (RAS) has been implicated in the pathogenesis of various cardiovascular diseases. Alamandine is a peptide newly identified as a protective component of the RAS; however, the mechanisms involved in its beneficial effects remain elusive. By using a well-characterized rat model of hypertension, the TGR (mREN2)27, we show that mREN ventricular myocytes are prone to contractile enhancement mediated by short-term alamandine (100 nmol\/L) stimulation of Mas-related G protein-coupled receptor member D (MrgD) receptors, while Sprague-Dawley control cells showed no effect. Additionally, alamandine prevents the Ca<jats:sup>2+<\/jats:sup> dysregulation classically exhibited by freshly isolated mREN myocytes. Accordingly, alamandine treatment of mREN myocytes attenuated Ca<jats:sup>2+<\/jats:sup> spark rate and enhanced Ca<jats:sup>2+<\/jats:sup> reuptake to the sarcoplasmic reticulum. Along with these findings, KN-93 fully inhibited the alamandine-induced increase in Ca<jats:sup>2+<\/jats:sup> transient magnitude and phospholamban (PLN) phosphorylation at Thr17, indicating CaMKII as a downstream effector of the MrgD signaling pathway. In mREN ventricular myocytes, alamandine treatment induced significant nitric oxide (NO) production. Importantly, NO synthase inhibition prevented the contractile actions of alamandine, including PLN-Thr17 phosphorylation at the CaMKII site, thereby indicating that NO acts upstream of CaMKII in the alamandine downstream signaling. Altogether, our results show that enhanced contractile responses mediated by alamandine in cardiomyocytes from hypertensive rats occur through a NO-dependent activation of CaMKII. <\/jats:p>","DOI":"10.1152\/ajpcell.00153.2019","type":"journal-article","created":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T21:22:19Z","timestamp":1578518539000},"page":"C740-C750","source":"Crossref","is-referenced-by-count":34,"title":["Alamandine enhances cardiomyocyte contractility in hypertensive rats through a nitric oxide-dependent activation of CaMKII"],"prefix":"10.1152","volume":"318","author":[{"given":"Itamar Couto Guedes","family":"Jesus","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"},{"name":"National Institute of Science and Technology in Nanobiopharmaceutics, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Th\u00e1ssio Ricardo Ribeiro","family":"Mesquita","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Lu\u00eds Lima","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda Borges","family":"Parreira","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson Kenedy","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizeu Lucas Xavier","family":"Coelho","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rio Morais","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas A. 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