{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:25:56Z","timestamp":1791199556699,"version":"4.2.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,12,22]]},"abstract":"<jats:p>\n                    The classically recognized functions of the renin\u2013angiotensin system are mediated by type 1 (AT\n                    <jats:sub>1<\/jats:sub>\n                    ) angiotensin receptors. Whereas man possesses a single AT\n                    <jats:sub>1<\/jats:sub>\n                    receptor, there are two AT\n                    <jats:sub>1<\/jats:sub>\n                    receptor isoforms in rodents (AT\n                    <jats:sub>1A<\/jats:sub>\n                    and AT\n                    <jats:sub>1B<\/jats:sub>\n                    ) that are products of separate genes (\n                    <jats:italic>Agtr1a<\/jats:italic>\n                    and\n                    <jats:italic>Agtr1b<\/jats:italic>\n                    ). We have generated mice lacking AT\n                    <jats:sub>1B<\/jats:sub>\n                    (\n                    <jats:italic>Agtr1b<\/jats:italic>\n                    \u2212\/\u2212) and both AT\n                    <jats:sub>1A<\/jats:sub>\n                    and AT\n                    <jats:sub>1B<\/jats:sub>\n                    receptors (\n                    <jats:italic>Agtr1a<\/jats:italic>\n                    \u2212\/\u2212\n                    <jats:italic>Agtr1b<\/jats:italic>\n                    \u2212\/\u2212).\n                    <jats:italic>Agtr1b<\/jats:italic>\n                    \u2212\/\u2212 mice are healthy, without an abnormal phenotype. In contrast,\n                    <jats:italic>Agtr1a<\/jats:italic>\n                    \u2212\/\u2212\n                    <jats:italic>Agtr1b<\/jats:italic>\n                    \u2212\/\u2212 mice have diminished growth, vascular thickening within the kidney, and atrophy of the inner renal medulla. This phenotype is virtually identical to that seen in angiotensinogen-deficient (\n                    <jats:italic>Agt<\/jats:italic>\n                    \u2212\/\u2212) and angiotensin-converting enzyme-deficient (\n                    <jats:italic>Ace<\/jats:italic>\n                    \u2212\/\u2212) mice that are unable to synthesize angiotensin II.\n                    <jats:italic>Agtr1a<\/jats:italic>\n                    \u2212\/\u2212\n                    <jats:italic>Agtr1b<\/jats:italic>\n                    \u2212\/\u2212 mice have no systemic pressor response to infusions of angiotensin II, but they respond normally to another vasoconstrictor, epinephrine. Blood pressure is reduced substantially in the\n                    <jats:italic>Agtr1a<\/jats:italic>\n                    \u2212\/\u2212\n                    <jats:italic>Agtr1b<\/jats:italic>\n                    \u2212\/\u2212 mice and following administration of an angiotensin converting enzyme inhibitor, their blood pressure increases paradoxically. We suggest that this is a result of interruption of AT\n                    <jats:sub>2<\/jats:sub>\n                    -receptor signaling. In summary, our studies suggest that both AT\n                    <jats:sub>1<\/jats:sub>\n                    receptors promote somatic growth and maintenance of normal kidney structure. The absence of either of the AT\n                    <jats:sub>1<\/jats:sub>\n                    receptor isoforms alone can be compensated in varying degrees by the other isoform. These studies reaffirm and extend the importance of AT\n                    <jats:sub>1<\/jats:sub>\n                    receptors to mediate physiological functions of the renin\u2013angiotensin system.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.26.15496","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:50Z","timestamp":1027679750000},"page":"15496-15501","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":269,"title":["Reduced growth, abnormal kidney structure, and type 2 (AT\n                    <sub>2<\/sub>\n                    ) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT\n                    <sub>1A<\/sub>\n                    and AT\n                    <sub>1B<\/sub>\n                    receptors for angiotensin II"],"prefix":"10.1073","volume":"95","author":[{"given":"Michael I.","family":"Oliverio","sequence":"first","affiliation":[{"name":"Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung-Suk","family":"Kim","sequence":"additional","affiliation":[{"name":"Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Ito","sequence":"additional","affiliation":[{"name":"Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thu","family":"Le","sequence":"additional","affiliation":[{"name":"Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Audoly","sequence":"additional","affiliation":[{"name":"Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher F.","family":"Best","sequence":"additional","affiliation":[{"name":"Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Hiller","sequence":"additional","affiliation":[{"name":"Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Kluckman","sequence":"additional","affiliation":[{"name":"Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyo","family":"Maeda","sequence":"additional","affiliation":[{"name":"Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7524; and School of Pharmaceutical Sciences, University of Shizuoka, Yada Shizuoka-Shi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Smithies","sequence":"additional","affiliation":[{"name":"Duke University and Durham Veterans Affairs Medical Centers, Durham, NC 27705; 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