{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T08:06:56Z","timestamp":1791878816549,"version":"4.3.4"},"reference-count":64,"publisher":"National Academy of Sciences","issue":"47","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,11,21]]},"abstract":"<jats:p>\n                    Essential hypertension is a common disease, yet its pathogenesis is not well understood. Altered control of sodium excretion in the kidney may be a key causative feature, but this has been difficult to test experimentally, and recent studies have challenged this hypothesis. Based on the critical role of the renin-angiotensin system (RAS) and the type I (AT\n                    <jats:sub>1<\/jats:sub>\n                    ) angiotensin receptor in essential hypertension, we developed an experimental model to separate AT\n                    <jats:sub>1<\/jats:sub>\n                    receptor pools in the kidney from those in all other tissues. Although actions of the RAS in a variety of target organs have the potential to promote high blood pressure and end-organ damage, we show here that angiotensin II causes hypertension primarily through effects on AT\n                    <jats:sub>1<\/jats:sub>\n                    receptors in the kidney. We find that renal AT\n                    <jats:sub>1<\/jats:sub>\n                    receptors are absolutely required for the development of angiotensin II-dependent hypertension and cardiac hypertrophy. When AT\n                    <jats:sub>1<\/jats:sub>\n                    receptors are eliminated from the kidney, the residual repertoire of systemic, extrarenal AT\n                    <jats:sub>1<\/jats:sub>\n                    receptors is not sufficient to induce hypertension or cardiac hypertrophy. Our findings demonstrate the critical role of the kidney in the pathogenesis of hypertension and its cardiovascular complications. Further, they suggest that the major mechanism of action of RAS inhibitors in hypertension is attenuation of angiotensin II effects in the kidney.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0605545103","type":"journal-article","created":{"date-parts":[[2006,11,7]],"date-time":"2006-11-07T22:59:07Z","timestamp":1162940347000},"page":"17985-17990","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":633,"title":["Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney"],"prefix":"10.1073","volume":"103","author":[{"given":"Steven D.","family":"Crowley","sequence":"first","affiliation":[{"name":"*Department of Medicine, Duke University Medical Center and Durham Veterans Affairs Medical Center, Durham, NC 27710;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan B.","family":"Gurley","sequence":"additional","affiliation":[{"name":"*Department of Medicine, Duke University 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