{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:31:12Z","timestamp":1792042272950,"version":"4.4.0"},"reference-count":75,"publisher":"Portland Press Ltd.","issue":"18","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Activation of the angiotensin (Ang)-converting enzyme (ACE) 2\/Ang-(1-7)\/MAS receptor pathway of the renin\u2013angiotensin system (RAS) induces protective mechanisms in different diseases. Herein, we describe the cardiovascular phenotype of a new transgenic rat line (TG7371) that expresses an Ang-(1-7)-producing fusion protein. The transgene-specific mRNA and the corresponding protein were shown to be present in all evaluated tissues of TG7371 with the highest expression in aorta and brain. Plasma Ang-(1-7) levels, measured by radioimmunoassay (RIA) were similar to control Sprague\u2013Dawley (SD) rats, however high Ang-(1-7) levels were found in the hypothalamus. TG7371 showed lower baseline mean arterial pressure (MAP), assessed in conscious or anesthetized rats by telemetry or short-term recordings, associated with increased plasma atrial natriuretic peptide (ANP) and higher urinary sodium concentration. Moreover, evaluation of regional blood flow and hemodynamic parameters with fluorescent microspheres showed a significant increase in blood flow in different tissues (kidneys, mesentery, muscle, spleen, brown fat, heart and skin), with a resulting decrease in total peripheral resistance (TPR). TG7371 rats, on the other hand, also presented increased cardiac and global sympathetic tone, increased plasma vasopressin (AVP) levels and decreased free water clearance. Altogether, our data show that expression of an Ang-(1-7)-producing fusion protein induced a hypotensive phenotype due to widespread vasodilation and consequent fall in peripheral resistance. This phenotype was associated with an increase in ANP together with an increase in AVP and sympathetic drive, which did not fully compensate the lower blood pressure (BP). Here we present the hemodynamic impact of long-term increase in tissue expression of an Ang-(1-7)-fusion protein and provide a new tool to investigate this peptide in different pathophysiological conditions.<\/jats:p>","DOI":"10.1042\/cs20210599","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T08:39:18Z","timestamp":1631090358000},"page":"2197-2216","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Hemodynamic phenotyping of transgenic rats with ubiquitous expression of an angiotensin-(1-7)-producing fusion protein"],"prefix":"10.1042","volume":"135","author":[{"given":"Daniele\u00a0T.","family":"Alves","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics and INCT-Nanobiopharmaceutics, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"},{"name":"Max-Delbr\u00fcck Center for Molecular Medicine-MDC, Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Beriln, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz\u00a0Felipe","family":"Mendes","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics and INCT-Nanobiopharmaceutics, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walkyria\u00a0O.","family":"Sampaio","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics and INCT-Nanobiopharmaceutics, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leda\u00a0M.C.","family":"Coimbra-Campos","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics and INCT-Nanobiopharmaceutics, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria\u00a0Aparecida\u00a0R.","family":"Vieira","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics and INCT-Nanobiopharmaceutics, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson\u00a0J.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Morphology, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almir\u00a0S.","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics and INCT-Nanobiopharmaceutics, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Popova","sequence":"additional","affiliation":[{"name":"Max-Delbr\u00fcck Center for Molecular Medicine-MDC, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihail","family":"Todiras","sequence":"additional","affiliation":[{"name":"Max-Delbr\u00fcck Center for Molecular Medicine-MDC, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatimunnisa","family":"Qadri","sequence":"additional","affiliation":[{"name":"Max-Delbr\u00fcck Center for Molecular Medicine-MDC, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Alenina","sequence":"additional","affiliation":[{"name":"Max-Delbr\u00fcck Center for Molecular Medicine-MDC, Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Beriln, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bader","sequence":"additional","affiliation":[{"name":"Max-Delbr\u00fcck Center for Molecular Medicine-MDC, Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Beriln, Germany"},{"name":"Institute for Biology, University of L\u00fcbeck, L\u00fcbeck, Germany"},{"name":"Charit\u00e9, University Medicine Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robson\u00a0A.S.","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics and INCT-Nanobiopharmaceutics, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9483-4206","authenticated-orcid":false,"given":"Maria\u00a0Jose","family":"Campagnole-Santos","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics and INCT-Nanobiopharmaceutics, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"2021113011234643400_B1","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1152\/physrev.00023.2016","article-title":"The ACE2\/Angiotensin-(1-7)\/MAS axis of the renin- angiotensin system: focus on angiotensin-(1-7)","volume":"98","author":"Santos","year":"2018","journal-title":"Physiol. Rev."},{"key":"2021113011234643400_B2","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1152\/physrev.00038.2017","article-title":"Angiotensin II signal transduction: an update on mechanisms of physiology and pathophysiology","volume":"98","author":"Forrester","year":"2018","journal-title":"Physiol. Rev."},{"key":"2021113011234643400_B3","first-page":"201","article-title":"Actions of angiotensin-(1-7): angiotensin-(1-7) and inflammation","volume-title":"Angiotensin-(1-7): A Comprehensive Review","author":"Galvao","year":"2019"},{"key":"2021113011234643400_B4","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1111\/j.1469-445X.2000.02096.x","article-title":"Transgenic animals in cardiovascular disease research","volume":"85","author":"Bader","year":"2000","journal-title":"Exp. Physiol."},{"key":"2021113011234643400_B5","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1111\/j.1365-201X.2004.01332.x","article-title":"Transgenic mice for studies of the renin-angiotensin system in hypertension","volume":"181","author":"Lavoie","year":"2004","journal-title":"Acta Physiol. Scand."},{"key":"2021113011234643400_B6","doi-asserted-by":"publisher","first-page":"11867","DOI":"10.1074\/jbc.273.19.11867","article-title":"Sustained long term potentiation and anxiety in mice lacking the MAS protooncogene","volume":"273","author":"Walther","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2021113011234643400_B7","doi-asserted-by":"publisher","first-page":"2218","DOI":"10.1172\/JCI16980","article-title":"Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice","volume":"116","author":"Gurley","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2021113011234643400_B8","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1161\/CIRCRESAHA.109.208645","article-title":"Brain-selective overexpression of human angiotensin-converting enzyme type 2 attenuates neurogenic hypertension","volume":"106","author":"Feng","year":"2010","journal-title":"Circ. Res."},{"key":"2021113011234643400_B9","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1152\/physiolgenomics.00227.2003","article-title":"Expression of an angiotensin- (1-7) producing fusion protein produces cardioprotective effects in rats","volume":"17","author":"Santos","year":"2004","journal-title":"Physiol. Genom."},{"key":"2021113011234643400_B10","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1177\/1753944709353426","article-title":"Attenuation of isoproterenol-induced cardiac fibrosis in transgenic rats harboring an angiotensin- (1-7)-producing fusion protein in the heart","volume":"4","author":"Ferreira","year":"2010","journal-title":"Ther. Adv. Cardiovasc. Dis."},{"key":"2021113011234643400_B11","doi-asserted-by":"publisher","first-page":"38S","DOI":"10.1016\/S0895-7061(01)02068-4","article-title":"Development and application of a biological peptide pump for the study of the in vivo actions of angiotensin peptides","volume":"14","author":"Methot","year":"2001","journal-title":"Am. J. Hypertens."},{"key":"2021113011234643400_B12","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1523\/JNEUROSCI.14-03-01030.1994","article-title":"GFAP promoter directs astrocyte-specific expression in transgenic mice","volume":"1","author":"Brenner","year":"1994","journal-title":"J. Neurosci."},{"key":"2021113011234643400_B13","doi-asserted-by":"publisher","first-page":"3975","DOI":"10.1073\/pnas.96.7.3975","article-title":"Blood pressure reduction and diabetes insipidus in transgenic rats deficient in brain angiotensinogen","volume":"96","author":"Schinke","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113011234643400_B14","first-page":"33","article-title":"Production of transgenic models in hypertension","volume":"108","author":"Popova","year":"2005","journal-title":"Methods Mol. Med."},{"key":"2021113011234643400_B15","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"2021113011234643400_B16","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/0196-9781(94)90103-1","article-title":"Plasma angiotensin-(1-7) immunoreactivity is increased by salt load, water deprivation, and hemorrhage","volume":"15","author":"Botelho","year":"1994","journal-title":"Peptides"},{"key":"2021113011234643400_B17","doi-asserted-by":"publisher","first-page":"R89","DOI":"10.1152\/ajpregu.1992.263.1.R89","article-title":"Differential baroreceptor reflex modulation by centrally infused angiotensin peptides","volume":"263","author":"Campagnole-Santos","year":"1992","journal-title":"Am. J. Physiol. Regul. Int. Comp. Physiol."},{"key":"2021113011234643400_B18","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1097\/00004872-200018120-00019","article-title":"Modulation of the baroreflex control of heart rate by angiotensin-(1-7) at the nucleus tractus solitarii of normotensive and spontaneously hypertensive rats","volume":"18","author":"Chaves","year":"2000","journal-title":"J. Hypertens."},{"key":"2021113011234643400_B19","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1161\/01.HYP.37.5.1309","article-title":"Baroreflex improvement in SHR after ACE inhibition involves angiotensin-(1-7)","volume":"37","author":"Heringer-Walther","year":"2001","journal-title":"Hypertension"},{"key":"2021113011234643400_B20","doi-asserted-by":"publisher","first-page":"H393","DOI":"10.1152\/ajpheart.00075.2012","article-title":"Chronic infusion of angiotensin-(1-7) into the lateral ventricle of the brain attenuates hypertension in DOCA-salt rats","volume":"303","author":"Guimaraes","year":"2012","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2021113011234643400_B21","doi-asserted-by":"publisher","first-page":"2585","DOI":"10.1152\/jappl.1993.74.5.2585","article-title":"Validation of fluorescent-labeled microspheres for measurement of regional organ perfusion","volume":"74","author":"Glenny","year":"1993","journal-title":"J. Appl. Physiol."},{"key":"2021113011234643400_B22","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1097\/00005344-199903000-00013","article-title":"Systemic and regional hemodynamics assessment in rats with fluorescent microspheres","volume":"33","author":"Gervais","year":"1999","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"2021113011234643400_B23","doi-asserted-by":"publisher","first-page":"H1985","DOI":"10.1152\/ajpheart.01145.2002","article-title":"Systemic and regional hemodynamic effects of angiotensin-(1-7) in rats","volume":"284","author":"Sampaio","year":"2003","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2021113011234643400_B24","doi-asserted-by":"publisher","first-page":"H2485","DOI":"10.1152\/ajpheart.01245.2006","article-title":"Expression of an angiotensin-(1-7)-producing fusion protein in rats induced marked changes in regional vascular resistance","volume":"292","author":"Botelho-Santos","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2021113011234643400_B25","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1161\/HYPERTENSIONAHA.117.09906","article-title":"Cyclooxygenase-2 selectively controls renal blood flow through a novel PPAR\u03b2\/\u03b4-dependent vasodilator pathway","volume":"71","author":"Kirkby","year":"2018","journal-title":"Hypertension"},{"key":"2021113011234643400_B26","doi-asserted-by":"publisher","first-page":"H725","DOI":"10.1152\/ajpheart.1995.269.2.H725","article-title":"Fluorescent microspheres to measure organ perfusion: validation of a simplified sample processing technique","volume":"269","author":"Van Oosterhout","year":"1995","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2021113011234643400_B27","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/344541a0","article-title":"Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene","volume":"344","author":"Mullins","year":"1990","journal-title":"Nature"},{"key":"2021113011234643400_B28","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.neuropharm.2015.04.036","article-title":"Activation of angiotensin-(1-7)\/MAS axis in the brain lowers blood pressure and attenuates cardiac remodeling in hypertensive transgenic (mRen2)27 rats","volume":"97","author":"Kangussu","year":"2015","journal-title":"Neuropharmacology"},{"key":"2021113011234643400_B29","first-page":"371","article-title":"Hypotensive function of the brain angiotensin-(1-7) in Sprague-Dawley and renin transgenic rats","volume":"54","author":"Dobruch","year":"2003","journal-title":"J. Physiol. Pharm."},{"key":"2021113011234643400_B30","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1161\/HYPERTENSIONAHA.113.01847","article-title":"Increasing angiotensin-(1-7) levels in the brain attenuates metabolic syndrome-related risks in fructose-fed rats","volume":"63","author":"Guimaraes","year":"2014","journal-title":"Hypertension"},{"key":"2021113011234643400_B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainres.2012.03.022","article-title":"Angiotensin-(1-7) upregulates central nitric oxide synthase in spontaneously hypertensive rats","volume":"1453","author":"Cerrato","year":"2012","journal-title":"Brain Res."},{"key":"2021113011234643400_B32","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1161\/01.HYP.0000259942.38108.20","article-title":"Overexpression of angiotensin-converting enzyme 2 in the rostral ventrolateral medulla causes long- term decrease in blood pressure in the spontaneously hypertensive rats","volume":"49","author":"Yamazato","year":"2007","journal-title":"Hypertension"},{"key":"2021113011234643400_B33","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1161\/HYPERTENSIONAHA.108.114322","article-title":"Transgenic angiotensin-converting enzyme 2 overexpression in vessels of SHRSP rats reduces blood pressure and improves endothelial function","volume":"52","author":"Rentzsch","year":"2008","journal-title":"Hypertension"},{"key":"2021113011234643400_B34","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1161\/HYPERTENSIONAHA.110.149815","article-title":"Lifetime overproduction of circulating angiotensin-(1-7) attenuates deoxycorticosterone acetate-salt hypertension-induced cardiac dysfunction and remodeling","volume":"55","author":"Santiago","year":"2010","journal-title":"Hypertension"},{"key":"2021113011234643400_B35","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.peptides.2013.11.006","article-title":"An orally active angiotensin-(1-7) inclusion compound and exercise training produce similar cardiovascular effects in spontaneously hypertensive rats","volume":"51","author":"Bertagnolli","year":"2014","journal-title":"Peptides"},{"key":"2021113011234643400_B36","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1097\/00005344-199711000-00019","article-title":"Angiotensin-(1-7) and the rat aorta: modulation by the endothelium","volume":"30","author":"Le Tran","year":"1997","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"2021113011234643400_B37","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0006-8993(00)02482-3","article-title":"Angiotensin-(1-7) causes endothelium-dependent relaxation in canine middle cerebral artery","volume":"873","author":"Feterik","year":"2000","journal-title":"Brain Res."},{"key":"2021113011234643400_B38","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1161\/01.HYP.37.2.703","article-title":"Potentiation of bradykinin by angiotensin-(1-7) on arterioles of spontaneously hypertensive rats studied in vivo","volume":"37","author":"Fernandes","year":"2001","journal-title":"Hypertension"},{"key":"2021113011234643400_B39","doi-asserted-by":"publisher","first-page":"H1416","DOI":"10.1152\/ajpheart.00141.2007","article-title":"Immunofluorescence localization of the receptor MAS in cardiovascular-related areas of the rat brain","volume":"293","author":"Becker","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2021113011234643400_B40","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/0304-3940(90)90063-F","article-title":"Autoradiographic localization of mas proto-oncogene mRNA in adult rat brain using in situ hybridization","volume":"114","author":"Bunnemann","year":"1990","journal-title":"Neurosci. Lett."},{"key":"2021113011234643400_B41","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/0014-5793(94)01292-9","article-title":"Expression of the mouse and rat MAS proto-oncogene in the brain and peripheral tissues","volume":"357","author":"Metzger","year":"1995","journal-title":"FEBS Lett."},{"key":"2021113011234643400_B42","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1016\/0196-9781(88)90208-2","article-title":"Immunocytochemical localization of angiotensin-(1-7) in the brain forebrain","volume":"9","author":"Block","year":"1988","journal-title":"Peptides"},{"key":"2021113011234643400_B43","doi-asserted-by":"publisher","first-page":"4095","DOI":"10.1073\/pnas.85.11.4095","article-title":"Release of vasopressin from the rat hypothalamo-neurohypophysial system by angiotensin- (1-7) heptapeptide","volume":"85","author":"Schiavone","year":"1988","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113011234643400_B44","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1097\/01.mnh.0000199008.49176.37","article-title":"The natriuretic peptide system: kidney and cardiovascular effects","volume":"15","author":"Silver","year":"2006","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"2021113011234643400_B45","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1056\/NEJMra1404726","article-title":"Molecular physiology of water balance","volume":"372","author":"Knepper","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"2021113011234643400_B46","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1042\/CS20120111","article-title":"Angiotensin-(1-7) in kidney disease: a review of the controversies","volume":"123","author":"Zimmerman","year":"2012","journal-title":"Clin. Sci. (Lond.)"},{"key":"2021113011234643400_B47","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/978-3-030-22696-1_8","article-title":"Actions of angiotensin-(1-7): kidney","volume-title":"Angiotensin-(1-7): A Comprehensive Review","author":"Sim\u00f5es e Silva","year":"2019"},{"key":"2021113011234643400_B48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1476-5381.1994.tb14014.x","article-title":"Natriuretic action of angiotensin-(1-7)","volume":"111","author":"Dellipizzi","year":"1994","journal-title":"Br. J. Pharmacol."},{"key":"2021113011234643400_B49","first-page":"651","article-title":"Angiotensin-(1-7) is a potent antidiuretic peptide in rats","volume":"25","author":"Santos","year":"1992","journal-title":"Braz. J. Med. Biol. Res."},{"key":"2021113011234643400_B50","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1681\/ASN.V541133","article-title":"Angiotensin-(1-7) has a biphasic effect on fluid absorption in the proximal straight tubule","volume":"5","author":"Garcia","year":"1994","journal-title":"J. Am. Soc. Nephrol."},{"key":"2021113011234643400_B51","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1161\/hy0302.104673","article-title":"Vasodilator action of angiotensin-(1-7) on isolated rabbit afferent arterioles","volume":"39","author":"Ren","year":"2002","journal-title":"Hypertension"},{"key":"2021113011234643400_B52","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.peptides.2017.02.001","article-title":"Angiotensin-(1-7)-dependent vasorelaxation of the renal artery exhibits unique angiotensin and bradykinin receptor selectivity","volume":"90","author":"Yousif","year":"2017","journal-title":"Peptides"},{"key":"2021113011234643400_B53","doi-asserted-by":"publisher","first-page":"961","DOI":"10.7150\/ijbs.20074","article-title":"Vasopressin mediates the renal damage induced by limited fructose rehydration in recurrently dehydrated rats","volume":"13","author":"Garc\u00eda-Arroyo","year":"2017","journal-title":"Int. J. Biol. Sci."},{"key":"2021113011234643400_B54","doi-asserted-by":"publisher","first-page":"5406","DOI":"10.1210\/jc.2019-01049","article-title":"Antidiuretic hormone and serum osmolarity physiology and related outcomes: what is old, what is new, and what is unknown?","volume":"104","author":"Kanbay","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2021113011234643400_B55","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1152\/physrev.1990.70.3.665","article-title":"Diverse biological actions of atrial natriuretic peptide","volume":"70","author":"Brenner","year":"1990","journal-title":"Physiol. Rev."},{"key":"2021113011234643400_B56","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/ng.328","article-title":"Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure","volume":"41","author":"Newton-Cheh","year":"2009","journal-title":"Nat. Genet."},{"key":"2021113011234643400_B57","doi-asserted-by":"publisher","first-page":"2850","DOI":"10.2337\/dc12-2337","article-title":"The atrial natriuretic peptide genetic variant rs5068 is associated with a favorable cardiometabolic phenotype in a Mediterranean population","volume":"36","author":"Cannone","year":"2013","journal-title":"Diabetes Care"},{"key":"2021113011234643400_B58","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1253\/circj.CJ-17-0499","article-title":"Atrial natriuretic peptide - Old but new therapeutic in cardiovascular diseases","volume":"81","author":"Ichiki","year":"2017","journal-title":"Circ. J."},{"key":"2021113011234643400_B59","first-page":"1036","article-title":"Atrial natriuretic peptide modulates sodium and potassium-activated adenosine triphosphatase through a mechanism involving cyclic GMP and cyclic GMP-dependent protein kinase","volume":"272","author":"Scavone","year":"1995","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2021113011234643400_B60","doi-asserted-by":"publisher","first-page":"R1093","DOI":"10.1152\/ajpregu.1984.247.6.R1093","article-title":"Release of natriuretic factor from rat heart-lung preparation by atrial distension","volume":"247","author":"Dietz","year":"1984","journal-title":"Am. J. Physiol. Regul. Int. Comp. Physiol."},{"key":"2021113011234643400_B61","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1038\/314264a0","article-title":"Atrial natriuretic factor-a circulating hormone stimulated by volume loading","volume":"314","author":"Lang","year":"1985","journal-title":"Nature"},{"key":"2021113011234643400_B62","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1152\/ajpheart.00608.2009","article-title":"Angiotensin-(1-7) stimulates high atrial pacing-induced ANP secretion via MAS\/PI3-kinase\/Akt axis and Na+\/H+ exchanger","volume":"298","author":"Shah","year":"2010","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2021113011234643400_B63","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1177\/1470320314543723","article-title":"Effects of the angiotensin-(1-7)\/MAS\/PI3K\/Akt\/nitric oxide axis and the possible role of atrial natriuretic peptide in an acute atrial tachycardia canine model","volume":"16","author":"Zhao","year":"2015","journal-title":"J. Renin Angiotensin Aldosterone Syst."},{"key":"2021113011234643400_B64","doi-asserted-by":"publisher","first-page":"11704","DOI":"10.1073\/pnas.94.21.11704","article-title":"Oxytocin releases atrial natriuretic peptide by combining with oxytocin receptors in the heart","volume":"94","author":"Gutkowska","year":"1997","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113011234643400_B65","doi-asserted-by":"publisher","first-page":"7902","DOI":"10.1073\/pnas.92.17.7902","article-title":"Oxytocin mediates atrial natriuretic peptide release and natriuresis after volume expansion in the rat","volume":"92","author":"Haanwinckel","year":"1995","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113011234643400_B66","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1161\/01.HYP.17.6.1111","article-title":"Neurophysiological responses to angiotensin-(1-7)","volume":"17","author":"Felix","year":"1991","journal-title":"Hypertension"},{"key":"2021113011234643400_B67","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/0306-4522(95)00238-E","article-title":"The association of thirst, sodium appetite and vasopressin release with c-Fos expression in the forebrain of the rat after intracerebroventricular injection of angiotensin II, angiotensin-(1-7) or carbachol","volume":"69","author":"Mahon","year":"1995","journal-title":"Neuroscience"},{"key":"2021113011234643400_B68","doi-asserted-by":"publisher","first-page":"I","DOI":"10.1161\/01.HYP.11.2_Pt_2.I75","article-title":"Baroreceptor reflex modulation by vasopressin microinjected into the nucleus tractus solitarii of conscious rats","volume":"11","author":"Michelini","year":"1988","journal-title":"Hypertension"},{"key":"2021113011234643400_B69","doi-asserted-by":"publisher","first-page":"R1073","DOI":"10.1152\/ajpregu.00572.2007","article-title":"Angiotensin-(1-7) serves as an aquaretic by increasing water intake and diuresis in association with downregulation of aquaporin-1 during pregnancy in rats","volume":"294","author":"Joyner","year":"2008","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2021113011234643400_B70","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1113\/EP086417","article-title":"Central angiotensin-(1-7) increases osmotic thirst","volume":"102","author":"Dos-Santos","year":"2017","journal-title":"Exp. Physiol."},{"key":"2021113011234643400_B71","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1161\/ATVBAHA.120.314078","article-title":"GFAP (Glial Fibrillary Acidic Protein)- positive progenitor cells contribute to the development of vascular smooth muscle cells and endothelial cells-brief report","volume":"40","author":"Osman","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2021113011234643400_B72","doi-asserted-by":"publisher","first-page":"12994","DOI":"10.1074\/jbc.272.20.12994","article-title":"Tissue targeting of angiotensin peptides","volume":"272","author":"Methot","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2021113011234643400_B73","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1074\/jbc.M209933200","article-title":"Brain- specific restoration of angiotensin II corrects renal defects seen in angiotensinogen-deficient mice","volume":"278","author":"Lochard","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2021113011234643400_B74","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1161\/01.CIR.0000144462.08345.B9","article-title":"Endothelium-restricted overexpression of human endothelin-1 causes vascular remodeling and endothelial dysfunction","volume":"110","author":"Amiri","year":"2004","journal-title":"Circulation"},{"key":"2021113011234643400_B75","doi-asserted-by":"publisher","first-page":"338","DOI":"10.3389\/fmed.2018.00338","article-title":"Chronic overexpression of bradykinin in kidney causes polyuria and cardiac hypertrophy","volume":"5","author":"Barros","year":"2018","journal-title":"Front. Med. (Lausanne)"}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/135\/18\/2197\/920944\/cs-2021-0599.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/135\/18\/2197\/920944\/cs-2021-0599.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T12:19:26Z","timestamp":1638274766000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/135\/18\/2197\/229735\/Hemodynamic-phenotyping-of-transgenic-rats-with"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":75,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2021,9,30]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20210599","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,9]]},"published":{"date-parts":[[2021,9]]}}}