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A mixed background strain with global deletion of the angiotensinogen gene was backcrossed to the FVB\/N background (Agt\u2010KO), a strain preferred for transgenic generation. Surprisingly, the resulting line turned out to be normotensive. Therefore, this study aimed to understand the unique blood pressure regulation of FVB\/N mice without angiotensin peptides.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Acute and chronic recordings of blood pressure (BP) in freely\u2010moving adult mice were performed to establish baseline BP. The pressure responses to sympatholytic and sympathomimetic as well as a nitric oxide inhibitor and donor compounds were used to quantify the neurogenic tone and endothelial function. The role of the renal nerves on baseline BP maintenance was tested by renal denervation. Finally, further phenotyping was done by gene expression analysis, histology and measurement of metabolites in plasma, urine and tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Baseline BP in adult FVB\/N Agt\u2010KO was unexpectedly unaltered. As compensatory mechanisms Agt\u2010KO presented an increased sympathetic nerve activity and reduced endothelial nitric oxide production. However, FVB\/N Agt\u2010KO exhibited the renal morphological and physiological alterations previously found in mice lacking the production of Ang II including polyuria and hydronephrosis. The hypotensive effect of bilateral renal denervation was blunted in Agt\u2010KO compared to wildtype FVB\/N mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>We describe a germline Agt\u2010KO line that challenges all previous knowledge on BP regulation in mice with deletion of the classical RAS. This line may represent a model of drug\u2010resistant hypertension because it lacks hypotension.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16051","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T04:08:35Z","timestamp":1675656515000},"page":"1843-1861","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Angiotensin deficient FVB\/N mice are normotensive"],"prefix":"10.1111","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7219-6896","authenticated-orcid":false,"given":"Andr\u00e9 Felipe","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine in the Helmholtz Association  Berlin Germany"},{"name":"Department of Biology, Chemistry and Pharmacy Free University of Berlin  Berlin Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihail","family":"Todiras","sequence":"additional","affiliation":[{"name":"Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine in the Helmholtz Association  Berlin Germany"},{"name":"Nicolae Testemi\u021banu State University of Medicine and Pharmacy  Chisinau Moldova"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatimunnisa","family":"Qadri","sequence":"additional","affiliation":[{"name":"Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine in the Helmholtz Association  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Alenina","sequence":"additional","affiliation":[{"name":"Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine in the Helmholtz Association  Berlin Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Bader","sequence":"additional","affiliation":[{"name":"Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine in the Helmholtz Association  Berlin Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Berlin  Berlin Germany"},{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Institute for Biology University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00007.2020"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15538"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07993"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.14069"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.010909.105610"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.12762"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07850"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00634-8"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2010.040"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.7326\/M17-3203"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab011"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1972.tb07259.x"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10557"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2020.03.003"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.00023"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003892200"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.3109\/10641968709160173"},{"issue":"5","key":"e_1_2_13_21_1","first-page":"953","article-title":"Mice lacking angiotensin\u2010converting enzyme have low blood pressure, renal pathology, and reduced male fertility","volume":"74","author":"Esther C. 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