{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:12:17Z","timestamp":1791486737860,"version":"4.3.4"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:p>Because of the presence of the blood\u2013brain barrier, brain renin\u2013angiotensin system activity should depend on local (pro)renin synthesis. Indeed, an intracellular form of renin has been described in the brain, but whether it displays angiotensin (Ang) I\u2013generating activity (AGA) is unknown. Here, we quantified brain (pro)renin, before and after buffer perfusion of the brain, in wild-type mice, renin knockout mice, deoxycorticosterone acetate salt\u2013treated mice, and Ang II\u2013infused mice. Brain regions were homogenized and incubated with excess angiotensinogen to detect AGA, before and after prorenin activation, using a renin inhibitor to correct for nonrenin-mediated AGA. Renin-dependent AGA was readily detectable in brain regions, the highest AGA being present in brain stem (&gt;thalamus=cerebellum=striatum=midbrain&gt;hippocampus=cortex). Brain AGA increased marginally after prorenin activation, suggesting that brain prorenin is low. Buffer perfusion reduced AGA in all brain areas by &gt;60%. Plasma renin (per mL) was 40\u00d7 to 800\u00d7 higher than brain renin (per gram). Renin was undetectable in plasma and brain of renin knockout mice. Deoxycorticosterone acetate salt and Ang II suppressed plasma renin and brain renin in parallel, without upregulating brain prorenin. Finally, Ang I was undetectable in brains of spontaneously hypertensive rats, while their brain\/plasma Ang II concentration ratio decreased by 80% after Ang II type 1 receptor blockade. In conclusion, brain renin levels (per gram) correspond with the amount of renin present in 1 to 20 \u03bcL of plasma. Brain renin disappears after buffer perfusion and varies in association with plasma renin. This indicates that brain renin represents trapped plasma renin. Brain Ang II represents Ang II taken up from blood rather than locally synthesized Ang II.<\/jats:p>","DOI":"10.1161\/hypertensionaha.116.08922","type":"journal-article","created":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T00:55:25Z","timestamp":1491872125000},"page":"1136-1144","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":83,"title":["Brain Renin\u2013Angiotensin System"],"prefix":"10.1161","volume":"69","author":[{"given":"Bibi S.","family":"van Thiel","sequence":"first","affiliation":[{"name":"From the Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (B.S.v.T., A.G.M., L.t.R., D.S., E.U., I.M.G., F.P.J.L., A.H.J.D.), Department of Vascular Surgery (B.S.v.T., L.t.R., I.v.d.P., J.E.), Department of Molecular Genetics, Cancer Genomics Center Netherlands (B.S.v.T., I.v.d.P., J.E.), Division of Nephrology and Transplantation, Department of Internal Medicine (D.S., E.U.), Department of Radiation Oncology (J.E.), Erasmus MC, Rotterdam, The Netherlands; Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"G\u00f3es Martini","sequence":"additional","affiliation":[{"name":"From the Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (B.S.v.T., A.G.M., L.t.R., D.S., E.U., I.M.G., F.P.J.L., A.H.J.D.), Department of Vascular Surgery (B.S.v.T., L.t.R., I.v.d.P., J.E.), Department of Molecular Genetics, Cancer Genomics Center Netherlands (B.S.v.T., I.v.d.P., J.E.), Division of Nephrology and Transplantation, Department of Internal Medicine (D.S., E.U.), Department of Radiation Oncology (J.E.), Erasmus MC, Rotterdam, The Netherlands; Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luuk","family":"te Riet","sequence":"additional","affiliation":[{"name":"From the Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (B.S.v.T., A.G.M., L.t.R., D.S., E.U., I.M.G., F.P.J.L., A.H.J.D.), Department of Vascular Surgery (B.S.v.T., L.t.R., I.v.d.P., J.E.), Department of Molecular Genetics, Cancer Genomics Center Netherlands (B.S.v.T., I.v.d.P., J.E.), Division of Nephrology and Transplantation, Department of Internal Medicine (D.S., E.U.), Department of Radiation Oncology (J.E.), Erasmus MC, Rotterdam, The Netherlands; Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Severs","sequence":"additional","affiliation":[{"name":"From the Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (B.S.v.T., A.G.M., L.t.R., D.S., E.U., I.M.G., F.P.J.L., A.H.J.D.), Department of Vascular Surgery (B.S.v.T., L.t.R., I.v.d.P., J.E.), Department of Molecular Genetics, Cancer Genomics Center Netherlands (B.S.v.T., I.v.d.P., J.E.), Division of Nephrology and Transplantation, Department of Internal Medicine (D.S., E.U.), Department of Radiation Oncology (J.E.), Erasmus MC, Rotterdam, The Netherlands; Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estrellita","family":"Uijl","sequence":"additional","affiliation":[{"name":"From the Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (B.S.v.T., A.G.M., L.t.R., D.S., E.U., I.M.G., F.P.J.L., A.H.J.D.), Department of Vascular Surgery (B.S.v.T., L.t.R., I.v.d.P., J.E.), Department of Molecular Genetics, Cancer Genomics Center Netherlands (B.S.v.T., I.v.d.P., J.E.), Division of Nephrology and Transplantation, Department of Internal Medicine (D.S., E.U.), Department of Radiation Oncology (J.E.), Erasmus MC, Rotterdam, The Netherlands; Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid M.","family":"Garrelds","sequence":"additional","affiliation":[{"name":"From the Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (B.S.v.T., A.G.M., L.t.R., D.S., E.U., I.M.G., F.P.J.L., A.H.J.D.), Department of Vascular Surgery (B.S.v.T., L.t.R., I.v.d.P., J.E.), Department of Molecular Genetics, Cancer Genomics Center Netherlands (B.S.v.T., I.v.d.P., J.E.), Division of Nephrology and Transplantation, Department of Internal Medicine (D.S., E.U.), Department of Radiation Oncology (J.E.), Erasmus MC, Rotterdam, The Netherlands; Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank P.J.","family":"Leijten","sequence":"additional","affiliation":[{"name":"From the Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (B.S.v.T., A.G.M., L.t.R., D.S., E.U., I.M.G., F.P.J.L., A.H.J.D.), Department of Vascular Surgery (B.S.v.T., L.t.R., I.v.d.P., J.E.), Department of Molecular Genetics, Cancer Genomics Center Netherlands (B.S.v.T., I.v.d.P., J.E.), Division of Nephrology and Transplantation, Department of Internal Medicine (D.S., E.U.), Department of Radiation Oncology (J.E.), Erasmus MC, Rotterdam, The Netherlands; Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"van der Pluijm","sequence":"additional","affiliation":[{"name":"From the Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (B.S.v.T., A.G.M., L.t.R., D.S., E.U., I.M.G., F.P.J.L., A.H.J.D.), Department of Vascular Surgery (B.S.v.T., L.t.R., I.v.d.P., J.E.), Department of Molecular Genetics, Cancer Genomics Center Netherlands (B.S.v.T., I.v.d.P., J.E.), Division of Nephrology and Transplantation, Department of Internal Medicine (D.S., E.U.), Department of Radiation Oncology (J.E.), Erasmus MC, Rotterdam, The Netherlands; Department..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Essers","sequence":"additional","affiliation":[{"name":"From the Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (B.S.v.T., A.G.M., L.t.R., D.S., E.U., I.M.G., F.P.J.L., A.H.J.D.), Department of Vascular Surgery (B.S.v.T., L.t.R., I.v.d.P., J.E.), Department of Molecular Genetics, Cancer Genomics Center Netherlands (B.S.v.T., I.v.d.P., J.E.), Division of Nephrology and Transplantation, Department of Internal Medicine (D.S., E.U.), Department of Radiation Oncology (J.E.), Erasmus MC, Rotterdam, The Netherlands; 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