{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T22:05:51Z","timestamp":1781042751608,"version":"3.54.1"},"reference-count":52,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:p>Hyperaldosteronism is linked to the development and progression of several different cardiovascular diseases. Angiotensin (Ang) II increases aldosterone secretion and adrenal blood flow. Ang II peptide fragments are produced by various peptidases, and these Angs have diverse and vital physiologic roles. Due to the uncharacteristic vasorelaxation of adrenal arteries by Ang II, we tested the hypothesis that Ang II metabolism contributes to its relaxant activity in adrenal arteries. Metabolism of Angs by bovine adrenal cortical arteries and isolated bovine adrenal vascular cells was measured by liquid chromatography-mass spectrometry. The primary Ang metabolites of adrenal arteries are Ang III and Ang (1\u20137), with Ang IV produced to a lesser extent. Bovine microvascular endothelial cells produced a similar metabolic profile to adrenal arteries, whereas bovine adrenal artery smooth muscle cells exhibited less metabolism. In preconstricted adrenal arteries, Ang II caused relaxation in picomolar concentrations and constrictions at 10nM. Ang-converting enzyme 2 inhibition augmented this relaxation response, whereas aminopeptidase inhibition did not. Ang III was equipotent to Ang II in relaxing adrenal arteries. Ang IV did not cause relaxation. Nitric oxide synthase inhibition enhanced Ang II-induced constriction of adrenal arteries. Aminopeptidase inhibition increased the concentration range for Ang II-induced constriction of adrenal arteries. Ang III and Ang IV did not change the basal tone but caused constriction of adrenal arteries with nitric oxide synthase inhibition. These data indicate that Ang II metabolism modulates the vascular effects of Ang II in the adrenal vasculature.<\/jats:p>","DOI":"10.1210\/en.2013-1160","type":"journal-article","created":{"date-parts":[[2013,10,4]],"date-time":"2013-10-04T02:01:35Z","timestamp":1380852095000},"page":"4768-4776","source":"Crossref","is-referenced-by-count":11,"title":["Endothelial Metabolism of Angiotensin II to Angiotensin III, not Angiotensin (1\u20137), Augments the Vasorelaxation Response in Adrenal Cortical Arteries"],"prefix":"10.1210","volume":"154","author":[{"given":"Phillip G.","family":"Kopf","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology (P.G.K., W.B.C.), Medical College of Wisconsin, Milwaukee, Wisconsin 53226"},{"name":"Department of Pharmacology (P.G.K.), Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois 60515"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Campbell","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology (P.G.K., W.B.C.), Medical College of Wisconsin, Milwaukee, Wisconsin 53226"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612563835900_B1","doi-asserted-by":"crossref","first-page":"2572","DOI":"10.1161\/CIRCULATIONAHA.106.668715","article-title":"Aldosterone and cardiovascular disease: smoke and fire","volume":"114","author":"Calhoun","year":"2006","journal-title":"Circulation"},{"key":"2020071612563835900_B2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s10741-005-2343-3","article-title":"Aldosterone biosynthesis, regulation, and classical mechanism of action","volume":"10","author":"Williams","year":"2005","journal-title":"Heart Fail Rev"},{"key":"2020071612563835900_B3","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1161\/01.HYP.0000040261.30455.B6","article-title":"Hyperaldosteronism among black and white subjects with resistant hypertension","volume":"40","author":"Calhoun","year":"2002","journal-title":"Hypertension"},{"key":"2020071612563835900_B4","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1046\/j.1440-1681.2001.03586.x","article-title":"Mineralocorticoids and cardiac fibrosis: the decade in review","volume":"28","author":"Funder","year":"2001","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"2020071612563835900_B5","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/0960-0760(91)90205-J","article-title":"The relationship between adrenal vascular events and steroid secretion: the role of mast cells and endothelin","volume":"40","author":"Hinson","year":"1991","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2020071612563835900_B6","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1677\/joe.0.1090279","article-title":"Effects of stimulation on steroid output and perfusion medium flow rate in the isolated perfused rat adrenal gland in situ","volume":"109","author":"Hinson","year":"1986","journal-title":"J Endocrinol"},{"key":"2020071612563835900_B7","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1677\/joe.0.1050285","article-title":"The mammalian adrenal circulation and the relationship between adrenal blood flow and steroidogenesis","volume":"105","author":"Vinson","year":"1985","journal-title":"J Endocrinol"},{"key":"2020071612563835900_B8","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0165-1838(90)90140-E","article-title":"Measurement of blood flow to the adrenal capsule, cortex and medulla in dogs after hemorrhage by fluorescent microspheres","volume":"30","author":"Jasper","year":"1990","journal-title":"J Auton Nerv Syst"},{"key":"2020071612563835900_B9","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S1043-2760(01)00381-2","article-title":"Angiotensin III: a central regulator of vasopressin release and blood pressure","volume":"12","author":"Reaux","year":"2001","journal-title":"Trends Endocrinol Metab"},{"key":"2020071612563835900_B10","first-page":"450","article-title":"Organ specificity of angiotensin II and des-aspartyl angiotensin II in the concious rat","volume":"198","author":"Campbell","year":"1976","journal-title":"J Phamacol Exp Ther"},{"key":"2020071612563835900_B11","first-page":"I-7","article-title":"Stimulation and inhibition of aldosterone biosynthesis in vitro by angiotensin II and analogs","volume":"34\/35","author":"Peach","year":"1974","journal-title":"Circ Res"},{"key":"2020071612563835900_B12","doi-asserted-by":"crossref","first-page":"R981","DOI":"10.1152\/ajpregu.00263.2003","article-title":"Effects of truncated angiotensins in humans after double blockade of the renin system","volume":"285","author":"Plovsing","year":"2003","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"2020071612563835900_B13","doi-asserted-by":"crossref","first-page":"R971","DOI":"10.1152\/ajpregu.00262.2003","article-title":"Effects of different angiotensins during acute, double blockade of the renin system in conscious dogs","volume":"285","author":"Wamberg","year":"2003","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"2020071612563835900_B14","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1038\/ki.1997.476","article-title":"Synthesis and effects of active fragments of angiotensin II","volume":"52","author":"Ardaillou","year":"1997","journal-title":"Kidney Int"},{"key":"2020071612563835900_B15","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1080\/1028415X.2001.11747381","article-title":"Differential effects of dietary cholesterol on aminopeptidase A, B and M in the frontal cortex of male and female mice","volume":"4","author":"Ram\u00edrez-Exp\u00f3sito","year":"2001","journal-title":"Nutr Neurosci"},{"key":"2020071612563835900_B16","doi-asserted-by":"crossref","first-page":"48623","DOI":"10.1074\/jbc.C100512200","article-title":"Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase","volume":"276","author":"Albiston","year":"2001","journal-title":"J Biol Chem"},{"key":"2020071612563835900_B17","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1097\/HJH.0b013e3283343250","article-title":"Renal vasoconstrictor and pressor responses to angiotensin IV in mice are AT1a-receptor mediated","volume":"28","author":"Yang","year":"2010","journal-title":"J Hypertens"},{"key":"2020071612563835900_B18","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1161\/01.RES.87.5.e1","article-title":"A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1\u20139","volume":"87","author":"Donoghue","year":"2000","journal-title":"Circ Res"},{"key":"2020071612563835900_B19","doi-asserted-by":"crossref","first-page":"F398","DOI":"10.1152\/ajprenal.90488.2008","article-title":"Localization of ACE2 in the renal vasculature: amplification by angiotensin II type 1 receptor blockade using telmisartan","volume":"296","author":"Soler","year":"2009","journal-title":"Am J Physiol Renal Physiol"},{"key":"2020071612563835900_B20","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0014-5793(02)03640-2","article-title":"Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme","volume":"532","author":"Harmer","year":"2002","journal-title":"FEBS Lett"},{"key":"2020071612563835900_B21","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1097\/00004872-199107000-00008","article-title":"Evidence that prolyl endopeptidase participates in the processing of brain angiotensin","volume":"9","author":"Welches","year":"1991","journal-title":"J Hypertens"},{"key":"2020071612563835900_B22","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1038\/2181224a0","article-title":"New enzymatic route for the inactivation of angiotensin","volume":"218","author":"Yang","year":"1968","journal-title":"Nature"},{"key":"2020071612563835900_B23","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1161\/01.HYP.0000196268.08909.fb","article-title":"Angiotensin-converting enzyme 2 and angiotensin-(1\u20137): an evolving story in cardiovascular regulation","volume":"47","author":"Ferrario","year":"2006","journal-title":"Hypertension"},{"key":"2020071612563835900_B24","doi-asserted-by":"crossref","first-page":"8258","DOI":"10.1073\/pnas.1432869100","article-title":"Angiotensin-(1\u20137) is an endogenous ligand for the G protein-coupled receptor Mas","volume":"100","author":"Santos","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612563835900_B25","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1507\/endocrj1954.32.767","article-title":"Pressor activity of angiotensin II-(2\u20137)-hexapeptide in man","volume":"32","author":"Kono","year":"1985","journal-title":"Endocrinol Jpn"},{"key":"2020071612563835900_B26","doi-asserted-by":"crossref","first-page":"16518","DOI":"10.1016\/S0021-9258(19)84737-3","article-title":"Identification of angiotensin-(1\u20137) in rat brain. Evidence for differential processing of angiotensin peptides","volume":"264","author":"Chappell","year":"1989","journal-title":"J Biol Chem"},{"key":"2020071612563835900_B27","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.regpep.2006.12.031","article-title":"Angiotensin-(3\u20137) pressor effect at the rostral ventrolateral medulla","volume":"141","author":"Ferreira","year":"2007","journal-title":"Regul Pept"},{"key":"2020071612563835900_B28","first-page":"F535","article-title":"Characterization of angiotensin IV-degrading enzymes and receptors on rat mesangial cells","volume":"275","author":"Chansel","year":"1998","journal-title":"Am J Physiol"},{"key":"2020071612563835900_B29","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/0196-9781(90)90095-M","article-title":"Processing of angiotensin peptides by NG108\u201315 neuroblastoma x glioma hybrid cell line","volume":"11","author":"Chappell","year":"1990","journal-title":"Peptides"},{"key":"2020071612563835900_B30","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1161\/01.HYP.4.2.178","article-title":"Brain endo-oligopeptidase B: a post-proline cleaving enzyme that inactivates angiotensin I and II","volume":"4","author":"Greene","year":"1982","journal-title":"Hypertension"},{"key":"2020071612563835900_B31","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1681\/ASN.V1181377","article-title":"Metabolism alters the selectivity of angiotensin-(1\u20137) receptor ligands for angiotensin receptors","volume":"11","author":"Handa","year":"2000","journal-title":"J Am Soc Nephrol"},{"key":"2020071612563835900_B32","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/0006-2952(95)02049-7","article-title":"Metabolism of angiotensin I in isolated rat hearts. Effect of angiotensin converting enzyme inhibitors","volume":"50","author":"Neves","year":"1995","journal-title":"Biochem Pharmacol"},{"key":"2020071612563835900_B33","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1161\/01.HYP.19.6.692","article-title":"In vivo metabolism of angiotensin I by neutral endopeptidase (EC 3.4.24.11) in spontaneously hypertensive rats","volume":"19","author":"Yamamoto","year":"1992","journal-title":"Hypertension"},{"key":"2020071612563835900_B34","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1161\/01.ATV.0000253889.09765.5f","article-title":"Mass-spectrometric identification of a novel angiotensin peptide in human plasma","volume":"27","author":"Jankowski","year":"2007","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2020071612563835900_B35","first-page":"S453","article-title":"Pressor and renal effects of angiotensin A","volume":"27","author":"Yang","year":"2009","journal-title":"J Hypertens"},{"key":"2020071612563835900_B36","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1210\/en.2005-0129","article-title":"Angiotensin II dilates bovine adrenal cortical arterioles: role of endothelial nitric oxide","volume":"146","author":"Gauthier","year":"2005","journal-title":"Endocrinology"},{"key":"2020071612563835900_B37","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1161\/HYPERTENSIONAHA.107.104158","article-title":"Angiotensin II relaxations of bovine adrenal cortical arteries: role of angiotensin II metabolites and endothelial nitric oxide","volume":"52","author":"Gauthier","year":"2008","journal-title":"Hypertension"},{"key":"2020071612563835900_B38","doi-asserted-by":"crossref","first-page":"5217","DOI":"10.1073\/pnas.76.10.5217","article-title":"Long-term culture of capillary endothelial cells","volume":"76","author":"Folkman","year":"1979","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612563835900_B39","doi-asserted-by":"crossref","first-page":"4411","DOI":"10.1210\/endo.140.10.7060","article-title":"Adrenal capillary endothelial cells stimulate aldosterone release through a protein that is distinct from endothelin","volume":"140","author":"Rosolowsky","year":"1999","journal-title":"Endocrinology"},{"key":"2020071612563835900_B40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ab.2007.06.045","article-title":"Simultaneous analysis of angiotensin peptides by LC-MS and LC-MS\/MS: metabolism by bovine adrenal endothelial cells","volume":"369","author":"Cui","year":"2007","journal-title":"Anal Biochem"},{"key":"2020071612563835900_B41","first-page":"957","article-title":"Binding, degradation and pressor activity of angiotensins II and III after aminopeptidase inhibition with amastatin and bestatin","volume":"242","author":"Abhold","year":"1987","journal-title":"J Pharmacol Exp Ther"},{"key":"2020071612563835900_B42","first-page":"643","article-title":"Role of aminopeptidase activity in the regulation of the pressor activity of circulating angiotensins","volume":"252","author":"Ahmad","year":"1990","journal-title":"J Pharmacol Exp Ther"},{"key":"2020071612563835900_B43","doi-asserted-by":"crossref","first-page":"II-166","DOI":"10.1161\/01.HYP.3.6_Pt_2.II-166","article-title":"Angiotensin I, II, and II tachyphylaxis in the mesenteric vascular circuit of the rat","volume":"3","author":"Fasciolo","year":"1981","journal-title":"Hypertension"},{"key":"2020071612563835900_B44","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1161\/01.HYP.20.2.151","article-title":"Distribution and metabolism of angiotensin I and II in the blood vessel wall","volume":"20","author":"Gohlke","year":"1992","journal-title":"Hypertension"},{"key":"2020071612563835900_B45","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1161\/01.HYP.33.2.746","article-title":"Kidney aminopeptidase A and hypertension, part II: effects of angiotensin II","volume":"33","author":"Song","year":"1999","journal-title":"Hypertension"},{"key":"2020071612563835900_B46","first-page":"F546","article-title":"Rat kidney glutamyl aminopeptidase (aminopeptidase A): molecular identity and cellular localization","volume":"267","author":"Song","year":"1994","journal-title":"Am J Physiol"},{"key":"2020071612563835900_B47","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1161\/01.HYP.0000196950.48596.21","article-title":"Renal angiotensin type 2 receptors mediate natriuresis via angiotensin III in the angiotensin II type 1 receptor-blocked rat","volume":"47","author":"Padia","year":"2006","journal-title":"Hypertension"},{"key":"2020071612563835900_B48","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1161\/HYPERTENSIONAHA.108.124198","article-title":"Intrarenal angiotensin III infusion induces natriuresis and angiotensin type 2 receptor translocation in Wistar-Kyoto but not in spontaneously hypertensive rats","volume":"53","author":"Padia","year":"2009","journal-title":"Hypertension"},{"key":"2020071612563835900_B49","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1161\/HYPERTENSIONAHA.107.103242","article-title":"Conversion of renal angiotensin II to angiotensin III is critical for AT2 receptor-mediated natriuresis in rats","volume":"51","author":"Padia","year":"2008","journal-title":"Hypertension"},{"key":"2020071612563835900_B50","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.cjca.2012.01.017","article-title":"Molecular mechanisms of hypertension-reactive oxygen species and antioxidants: a basic science update for the clinician","volume":"28","author":"Montezano","year":"2012","journal-title":"Can J Cardiol"},{"key":"2020071612563835900_B51","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1126\/science.184.4140.994","article-title":"Angiotensin II- and angiotensin 3-induced aldosterone release vivo in the rat","volume":"184","author":"Campbell","year":"1974","journal-title":"Science"},{"key":"2020071612563835900_B52","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1210\/en.2010-1070","article-title":"Angiotensin III stimulates aldosterone secretion from adrenal gland partially via angiotensin II type 2 receptor but not angiotensin II type 1 receptor","volume":"152","author":"Yatabe","year":"2011","journal-title":"Endocrinology"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/154\/12\/4768\/13636225\/endo4768.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/154\/12\/4768\/13636225\/endo4768.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T21:33:30Z","timestamp":1646688810000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/154\/12\/4768\/2433359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,1]]},"references-count":52,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2013,12,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2013-1160","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,1]]}}}