{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T06:50:25Z","timestamp":1776322225480,"version":"3.50.1"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[1997,4]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            The angiotensinogen gene is one of the very few related by linkage analysis to human hypertension, but the linkage has been consistently shown only among males. Moreover, polymorphisms in this gene predict an abnormal renal responsiveness to angiotensin II, a feature of non-modulation, but again, only among males. To pursue these related bridges between genetics and physiology, we evaluated the effects of sex on a second feature of non-modulation, the aldosterone response to infused angiotensin II during low sodium balance. We tested the resultant hypothesis\u2014that non-modulation would be less frequent in women\u2014by conducting identical protocols on 225 hypertensive inpatients (70 women, 155 men). Non-modulation was strikingly less frequent among women (26%; 95% confidence interval, 16% to 37%) than men (49%; 95% confidence interval, 40% to 57%) (\n            <jats:italic>P<\/jats:italic>\n            =.001). We tested the hypothesis that sex steroids play a role by comparing young, premenopausal women (&lt;35 years) with women who were perimenopausal (45 to 55 years) and postmenopausal (&gt;55 years). Among the youngest women, the frequency of non-modulation was only 7%, significantly less than in young men (41%,\n            <jats:italic>P<\/jats:italic>\n            =.02). A steady increase in non-modulation frequency accompanied advancing age in women, reaching 47% in those older than 55 years, equal to the fraction of men affected. Age influenced non-modulation frequency in men far less. We conclude that a striking sex difference underlies the non-modulation phenotype and that female sex hormones may confer protection against a genotypic predisposition in women. This \u201coverride\u201d of genotype, manifest by a very low frequency of non-modulation in young women, may participate in their known protection against cardiovascular disease.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.29.4.980","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"980-985","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":39,"title":["Age, Gender, and Non-modulation"],"prefix":"10.1161","volume":"29","author":[{"given":"Naomi D. L.","family":"Fisher","sequence":"first","affiliation":[{"name":"From the Departments of Medicine, Harvard Medical School and Brigham and Women\u2019s Hospital, Boston, Mass, and Universita\u0300 La Sapienza, Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Ferri","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, Harvard Medical School and Brigham and Women\u2019s Hospital, Boston, Mass, and Universita\u0300 La Sapienza, Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cesare","family":"Bellini","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, Harvard Medical School and Brigham and Women\u2019s Hospital, Boston, Mass, and Universita\u0300 La Sapienza, Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Santucci","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, Harvard Medical School and Brigham and Women\u2019s Hospital, Boston, Mass, and Universita\u0300 La Sapienza, Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ray","family":"Gleason","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, Harvard Medical School and Brigham and Women\u2019s Hospital, Boston, Mass, and Universita\u0300 La Sapienza, Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon H.","family":"Williams","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, Harvard Medical School and Brigham and Women\u2019s Hospital, Boston, Mass, and Universita\u0300 La Sapienza, Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norman K.","family":"Hollenberg","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, Harvard Medical School and Brigham and Women\u2019s Hospital, Boston, Mass, and Universita\u0300 La Sapienza, Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen W.","family":"Seely","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine, Harvard Medical School and Brigham and Women\u2019s Hospital, Boston, Mass, and Universita\u0300 La Sapienza, Rome, Italy."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","first-page":"181","volume":"6","year":"1996","unstructured":"Chen YF. Sexual dimorphism of hypertension. Curr Opin Nephrol Hypertens. 1996;6:181-185.","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90275-H"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199602000-00008"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.11.1.49"},{"key":"e_1_3_2_5_2","first-page":"632","volume":"81","year":"1973","unstructured":"Emanuel R, Cain JP, Williams GH. Double antibody radioimmunoassay of renin activity and angiotensin II in human peripheral plasma. J Lab Clin Med. 1973;81:632-640.","journal-title":"J Lab Clin Med"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","unstructured":"Williams GH Hollenberg NK. Are non-modulating patients with essential hypertension a distinct subgroup? 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