{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:07:10Z","timestamp":1769213230210,"version":"3.49.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[1997,7]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>Angiotensin II (Ang II) is internalized by various cell types via receptor-mediated endocytosis. Little is known about the kinetics of this process in the whole animal and about the half-life of intact Ang II after its internalization. We measured the levels of<jats:sup>125<\/jats:sup>I\u2013Ang II and<jats:sup>125<\/jats:sup>I\u2013Ang I that were reached in various tissues and blood plasma during infusions of these peptides into the left cardiac ventricle of pigs. Steady-state concentrations of<jats:sup>125<\/jats:sup>I\u2013Ang II in skeletal muscle, heart, kidney, and adrenal were 8% to 41%, 64% to 150%, 340% to 550%, and 680% to 2100%, respectively, of the<jats:sup>125<\/jats:sup>I\u2013Ang II concentration in arterial blood plasma (ranges of six experiments). The tissue concentrations of<jats:sup>125<\/jats:sup>I\u2013Ang I were less than 5% of the arterial plasma concentrations.<jats:sup>125<\/jats:sup>I\u2013Ang II accumulation seen in heart, kidney, and adrenal was almost completely blocked by a specific Ang II type 1 (AT<jats:sub>1<\/jats:sub>) receptor antagonist. Steady-state concentrations of<jats:sup>125<\/jats:sup>I\u2013Ang II were reached within 30 to 60 minutes in the tissues and within 5 minutes in blood plasma. The in vivo half-life of intact<jats:sup>125<\/jats:sup>I\u2013Ang II in heart, kidney, and adrenal was approximately 15 minutes, compared with 0.5 minute in the circulation. Thus, Ang II, but not Ang I, from the circulation is accumulated by some tissues, and this is mediated by AT<jats:sub>1<\/jats:sub>receptors. The time course of this process and the long half-life of the accumulated Ang II support the contention that this Ang II has been internalized after its binding to the AT<jats:sub>1<\/jats:sub>receptor, so that it is protected from rapid degradation by endothelial peptidases. The results of this study are in agreement with growing evidence of an important physiological role for internalized Ang II.<\/jats:p>","DOI":"10.1161\/01.hyp.30.1.42","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"42-49","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":139,"title":["Angiotensin II Type 1 (AT<sub>1<\/sub>) Receptor\u2013Mediated Accumulation of Angiotensin II in Tissues and Its Intracellular Half-life In Vivo"],"prefix":"10.1161","volume":"30","author":[{"given":"Jorge P.","family":"van Kats","sequence":"first","affiliation":[{"name":"From the Departments of Internal Medicine (J.P. van K., L.M. de L., M.A.D.H.S.), Experimental Cardiology (J.P. van K., J.R. van M., P.D.V.), and Pharmacology (L.M. de L., A.H.J.D.), Cardiovascular Research Institute Erasmus University Rotterdam (COEUR) (the Netherlands)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larissa M.","family":"de Lannoy","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.P. van K., L.M. de L., M.A.D.H.S.), Experimental Cardiology (J.P. van K., J.R. van M., P.D.V.), and Pharmacology (L.M. de L., A.H.J.D.), Cardiovascular Research Institute Erasmus University Rotterdam (COEUR) (the Netherlands)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. H. Jan","family":"Danser","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.P. van K., L.M. de L., M.A.D.H.S.), Experimental Cardiology (J.P. van K., J.R. van M., P.D.V.), and Pharmacology (L.M. de L., A.H.J.D.), Cardiovascular Research Institute Erasmus University Rotterdam (COEUR) (the Netherlands)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan R.","family":"van Meegen","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.P. van K., L.M. de L., M.A.D.H.S.), Experimental Cardiology (J.P. van K., J.R. van M., P.D.V.), and Pharmacology (L.M. de L., A.H.J.D.), Cardiovascular Research Institute Erasmus University Rotterdam (COEUR) (the Netherlands)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter D.","family":"Verdouw","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.P. van K., L.M. de L., M.A.D.H.S.), Experimental Cardiology (J.P. van K., J.R. van M., P.D.V.), and Pharmacology (L.M. de L., A.H.J.D.), Cardiovascular Research Institute Erasmus University Rotterdam (COEUR) (the Netherlands)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maarten A. D. H.","family":"Schalekamp","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.P. van K., L.M. de L., M.A.D.H.S.), Experimental Cardiology (J.P. van K., J.R. van M., P.D.V.), and Pharmacology (L.M. de L., A.H.J.D.), Cardiovascular Research Institute Erasmus University Rotterdam (COEUR) (the Netherlands)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.25.5.924"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114244"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1993.264.1.C179"},{"key":"e_1_3_2_4_2","first-page":"2471","volume":"90","year":"1992","unstructured":"Schelling JR, Hanson AS, Marzec R, Linas SL. Cytoskeleton-dependent endocytosis is required for apical type 1 angiotensin II receptor-mediated phospholipase C activation in cultured rat proximal tubule cells. J Clin Invest. 1992;90:2471-2480.","journal-title":"J Clin Invest"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-118-6-2605"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-119-4-1873"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-118-6-2312"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-0115(94)90161-9"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47832-5"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)49915-2"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3109\/07435809509030437"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-125-5-2463"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.2603"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.6.1679"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)84973-6"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.172.3988.1138"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.131.1.1612017"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1430449"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(84)91641-3"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(84)90228-5"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.22.4.496"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199109010-00002"},{"key":"e_1_3_2_23_2","first-page":"H418","volume":"263","year":"1992","unstructured":"Danser AHJ, Koning MMG, Admiraal PJJ, Derkx FHM, Verdouw PD, Schalekamp MADH. Metabolism of angiotensin I by different tissues in the intact animal. Am J Physiol. 1992;263:H418-H428.","journal-title":"Am J Physiol"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1992.263.2.C429"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.15.1.44"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.24.1.37"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0022-3565(25)10725-8","volume":"262","year":"1992","unstructured":"Chang RSL, Siegl PKS, Clineschmidt BV, Mantlo NB, Chakravarty PK, Greenlee WJ, Patchett AA, Lotti VJ. In vitro pharmacology of L-158,809, a new highly potent and selective angiotensin II receptor antagonist. J Pharmacol Exp Ther. 1992;262:133-138.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0022-3565(25)10726-X","volume":"262","year":"1992","unstructured":"Siegl PKS, Chang RSL, Mantlo NB, Chakravarty PK, Ondeyka DL, Greenlee WJ, Patchett AA, Sweet CS, Lotti VJ. In vivo pharmacology of L-158,809, a new highly potent and selective nonpeptide angiotensin II receptor antagonist. J Pharmacol Exp Ther. 1992;262:139-144.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15277.x"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.21.2.173"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)31462-X"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(89)92133-5"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199507000-00011"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1994.tb02555.x"},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/S0022-3565(25)22415-6","volume":"270","year":"1994","unstructured":"Nozawa Y, Haruno A, Oda N, Yamasaki Y, Matsuura N, Yamada S, Inabe K, Kimura R, Suzuki H, Hoshino T. Angiotensin II receptor subtypes in bovine and human ventricular myocardium. J Pharmacol Exp Ther. 1994;270:566-571.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.91.5.1461"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.27.3.658"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.28.4.669"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.HYP.30.1.42","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T22:11:08Z","timestamp":1743372668000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.HYP.30.1.42"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,7]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1997,7]]}},"alternative-id":["10.1161\/01.HYP.30.1.42"],"URL":"https:\/\/doi.org\/10.1161\/01.hyp.30.1.42","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,7]]},"assertion":[{"value":"1996-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1996-12-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1997-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}