{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T10:54:13Z","timestamp":1768560853067,"version":"3.49.0"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,8,5]],"date-time":"2014-08-05T00:00:00Z","timestamp":1407196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Hypertension is a major clinical complication of obesity. Our previous studies show that abnormal uptake of the nitric oxide precursor <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>\u2010arginine, via the cationic amino acid transporter\u20101 (<jats:styled-content style=\"fixed-case\">CAT<\/jats:styled-content>1), contributes to endothelial dysfunction in cardiovascular disease. In this study, we tested the hypothesis that abnormal <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>\u2010arginine transport may be a key mediator of obesity\u2010induced hypertension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mean arterial pressure (<jats:styled-content style=\"fixed-case\">MAP<\/jats:styled-content>) was monitored by telemetry in conscious wild\u2010type (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>;<jats:italic> n<\/jats:italic>\u00a0=\u00a013) mice, and transgenic mice with endothelial\u2010specific overexpression of <jats:styled-content style=\"fixed-case\">CAT<\/jats:styled-content>1 (<jats:styled-content style=\"fixed-case\">CAT<\/jats:styled-content>+; <jats:italic>n<\/jats:italic>\u00a0=\u00a014) fed a normal or a high fat diet for 20\u00a0weeks. Renal angiotensin <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>ng <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">CAT<\/jats:styled-content>1 m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> and plasma nitrate\/nitrite levels were then quantified. In conjunction, plasma nitrate\/nitrite levels were assessed in obese normotensive (<jats:italic>n<\/jats:italic>\u00a0=\u00a015) and obese hypertensive subjects (<jats:italic>n<\/jats:italic>\u00a0=\u00a015).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both genotypes of mice developed obesity when fed a high fat diet (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.002). Fat fed <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> mice had 13% greater <jats:styled-content style=\"fixed-case\">MAP<\/jats:styled-content> and 78% greater renal <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>ng <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> content, 42% lesser renal <jats:styled-content style=\"fixed-case\">CAT<\/jats:styled-content>1 m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> levels and 42% lesser plasma nitrate\/nitrite levels, than <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> mice fed a normal fat diet (<jats:italic>P\u00a0<\/jats:italic>\u2264<jats:italic>\u00a0<\/jats:italic>0.02). In contrast, none of these variables were significantly altered by high fat feeding in <jats:styled-content style=\"fixed-case\">CAT<\/jats:styled-content>+ mice (<jats:italic>P\u00a0<\/jats:italic>\u2265<jats:italic>\u00a0<\/jats:italic>0.36). Plasma nitrate\/nitrite levels were 17% less in obese hypertensives compared with obese normotensives (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.02).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Collectively, these data indicate that obesity\u2010induced down\u2010regulation of <jats:styled-content style=\"fixed-case\">CAT<\/jats:styled-content>1 expression and subsequent reduced bioavailability of nitric oxide may contribute to the development of obesity\u2010induced hypertension.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.12344","type":"journal-article","created":{"date-parts":[[2014,7,10]],"date-time":"2014-07-10T15:22:49Z","timestamp":1405005769000},"page":"39-48","source":"Crossref","is-referenced-by-count":30,"title":["Augmented endothelial\u2010specific <scp>L<\/scp>\u2010arginine transport prevents obesity\u2010induced hypertension"],"prefix":"10.1111","volume":"212","author":[{"given":"N. W.","family":"Rajapakse","sequence":"first","affiliation":[{"name":"Baker IDI Heart and Diabetes Institute Melbourne Vic. Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Karim","sequence":"additional","affiliation":[{"name":"Baker IDI Heart and Diabetes Institute Melbourne Vic. Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. E.","family":"Straznicky","sequence":"additional","affiliation":[{"name":"Baker IDI Heart and Diabetes Institute Melbourne Vic. Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Baker IDI Heart and Diabetes Institute Melbourne Vic. Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. G.","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Physiology Monash University Melbourne Vic. Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. A.","family":"Head","sequence":"additional","affiliation":[{"name":"Baker IDI Heart and Diabetes Institute Melbourne Vic. Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. M.","family":"Kaye","sequence":"additional","affiliation":[{"name":"Baker IDI Heart and Diabetes Institute Melbourne Vic. 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