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However, the mechanisms responsible for this sexual dimorphism are unknown. The current study tested the hypothesis that sex differences in renal<jats:styled-content style=\"fixed-case\">IM NOS<\/jats:styled-content>activity and<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>1 expression in adult<jats:styled-content style=\"fixed-case\">SHRs<\/jats:styled-content>develop with sexual maturation and increases in blood pressure (BP) in a female sex hormone\u2010dependent manner.<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Methods and Results<\/jats:title><jats:p xml:lang=\"en\">Renal<jats:styled-content style=\"fixed-case\">IM<\/jats:styled-content>were isolated from sexually immature 5\u2010week\u2010old and sexually mature 13\u2010week\u2010old male and female<jats:styled-content style=\"fixed-case\">SHRs<\/jats:styled-content>. Whereas<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>activity and<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>1 expression were comparable in 5\u2010\u00a0and 13\u2010week\u2010old male<jats:styled-content style=\"fixed-case\">SHRs<\/jats:styled-content>and 5\u2010week\u2010old female<jats:styled-content style=\"fixed-case\">SHRs<\/jats:styled-content>, 13\u2010week\u2010old females had greater<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>activity and<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>1 expression, compared to 5\u2010week\u2010old female<jats:styled-content style=\"fixed-case\">SHRs<\/jats:styled-content>and age\u2010matched males.<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>3 expression was greater in 5\u2010week\u2010old than 13\u2010week\u2010old<jats:styled-content style=\"fixed-case\">SHRs<\/jats:styled-content>regardless of sex. Treatment with antihypertensive therapy (hydrochlorothiazide and reserpine) from 6 to 12\u00a0weeks of age to attenuate age\u2010related increases in BP abolished the sex difference in<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>activity and<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>1 expression between sexually mature<jats:styled-content style=\"fixed-case\">SHR<\/jats:styled-content>males and females. To assess the role of female sex hormones in age\u2010related increases in<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>, additional females were ovariectomized (<jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>), and<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>activity was studied 8\u00a0weeks post\u2010<jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>.<jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>decreased<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>activity and<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>1 expression.<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Conclusions<\/jats:title><jats:p xml:lang=\"en\">The sex difference in renal<jats:styled-content style=\"fixed-case\">IM NOS<\/jats:styled-content>in<jats:styled-content style=\"fixed-case\">SHR<\/jats:styled-content>is mediated by a sex hormone\u2010 and BP\u2010dependent increase in<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>1 expression and<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>activity exclusively in females.<\/jats:p><\/jats:sec>","DOI":"10.1161\/jaha.114.001738","type":"journal-article","created":{"date-parts":[[2015,4,11]],"date-time":"2015-04-11T01:42:51Z","timestamp":1428716571000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Blood Pressure, Sex, and Female Sex Hormones Influence Renal Inner Medullary Nitric Oxide Synthase Activity and Expression in Spontaneously Hypertensive Rats"],"prefix":"10.1161","volume":"4","author":[{"given":"Jennifer M.","family":"Sasser","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystal N.","family":"Brinson","sequence":"additional","affiliation":[{"name":"Department of Physiology, Georgia Regents University, Augusta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlee J.","family":"Tipton","sequence":"additional","affiliation":[{"name":"Department of Physiology, Georgia Regents University, Augusta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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