{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:47:17Z","timestamp":1774532837435,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2013,7,15]],"date-time":"2013-07-15T00:00:00Z","timestamp":1373846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic syndrome is associated with an increased risk of colorectal  cancer. This study investigated the impact of hypertension, a component of metabolic syndrome, on azoxymethane (AOM)-induced colorectal carcinogenesis using  SHRSP\/Izm (SHRSP) non-diabetic\/hypertensive rats and SHRSP.Z-Leprfa\/IzmDmcr (SHRSP-ZF) diabetic\/hypertensive rats. Male 6-week-old SHRSP, SHRSP-ZF, and control non-diabetic\/normotensive Wister Kyoto\/Izm (WKY) rats were given 2 weekly intraperitoneal injections of AOM (20 mg\/kg body weight). Two weeks after the last injection of AOM, the SHRSP and SHRSP-ZF rats became hypertensive compared to the control WKY rats. Serum levels of angiotensin-II, the active product of the renin-angiotensin system, were elevated in both SHRSP and SHRSP-ZF rats, but only the SHRSP-ZF rats developed insulin resistance, dyslipidemia, and hyperleptinemia and exhibited an increase in adipose tissue. The development of AOM-induced colonic preneoplastic lesions and aberrant crypts foci, was significantly accelerated in both SHRSP and SHRSP-ZF hypertensive rats, compared to WKY normotensive rats. Furthermore, induction of oxidative stress and exacerbation of inflammation were observed in the colonic mucosa and systemically in SHRSP and SHRSP-ZF rats. Our findings suggest that hypertension plays a role in the early stage of colorectal carcinogenesis by inducing oxidative stress and chronic inflammation, which might be associated with activation of the renin-angiotensin system.<\/jats:p>","DOI":"10.3390\/ijms140714700","type":"journal-article","created":{"date-parts":[[2013,7,15]],"date-time":"2013-07-15T11:25:32Z","timestamp":1373887532000},"page":"14700-14711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats"],"prefix":"10.3390","volume":"14","author":[{"given":"Takahiro","family":"Kochi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahito","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiko","family":"Ohno","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Baba","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takafumi","family":"Sumi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaya","family":"Kubota","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Shirakami","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Tsurumi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuji","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisataka","family":"Moriwaki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2013,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/S0140-6736(05)67402-8","article-title":"The metabolic syndrome\u2014A new worldwide definition","volume":"366","author":"Alberti","year":"2005","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1161\/CIRCULATIONAHA.105.169404","article-title":"Diagnosis and management of the metabolic syndrome: An American Heart Association\/National Heart, Lung, and Blood Institute Scientific Statement","volume":"112","author":"Grundy","year":"2005","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/cncr.21950","article-title":"The metabolic syndrome and risk of incident colorectal cancer","volume":"107","author":"Ahmed","year":"2006","journal-title":"Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1161\/HYPERTENSIONAHA.111.189258","article-title":"Blood pressure and risk of cancer incidence and mortality in the Metabolic Syndrome and Cancer Project","volume":"59","author":"Stocks","year":"2012","journal-title":"Hypertension"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ishino, K., Mutoh, M., Totsuka, Y., and Nakagama, H. 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