{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:37:24Z","timestamp":1791146244049,"version":"4.1.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2001,2]]},"abstract":"<jats:p>\n            Endothelial  dysfunction is associated with hypertension,  hypercholesterolemia, and heart failure. We  tested the hypothesis that spontaneously diabetic Goto-Kakizaki (GK)  rats, a model for type 2 diabetes, exhibit endothelial  dysfunction. Rats also received a high-sodium diet (6% NaCl [wt\/wt])  and chronic angiotensin type 1 (AT\n            <jats:sub>1<\/jats:sub>\n            )  receptor blockade (10 mg\/kg PO valsartan for 8 weeks). Compared with  age-matched nondiabetic Wistar control rats, GK rats had higher blood  glucose levels (9.3\u00b10.5 versus 6.9\u00b10.2 mmol\/L for control rats),  2.7-fold higher serum insulin levels, and impaired glucose tolerance  (all\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05).  Telemetry-measured mean blood pressure was 15 mm Hg higher in GK  rats (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01) compared with  control rats, whereas heart rates were not different. Heart weight\u2013  and kidney weight\u2013to\u2013body weight ratios were higher in GK rats  (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05), and 24-hour  albuminuria was increased 50%.  Endothelium-mediated relaxation of  noradrenaline-precontracted mesenteric arterial  rings by acetylcholine was impaired compared with the control condition  (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05), whereas the sodium  nitroprusside\u2013induced relaxation was similar. Preincubation of the  arterial rings with the NO synthase inhibitor\n            <jats:italic>N<\/jats:italic>\n            <jats:sup>G<\/jats:sup>\n            -nitro-\n            <jats:sc>l<\/jats:sc>\n            -arginine  methyl ester and the cyclooxygenase  inhibitor diclofenac inhibited relaxations to acetylcholine  almost completely in GK rats but not in Wistar rats, suggesting that  endothelial dysfunction can be in part attributed to  reduced relaxation via arterial  K\n            <jats:sup>+<\/jats:sup>\n            channels. Perivascular  monocyte\/macrophage infiltration and intercellular adhesion  molecule-1 overexpression were observed in GK rat kidneys. A  high-sodium diet increased blood pressure by 24 mm Hg and 24-hour  albuminuria by 350%, induced cardiac  hypertrophy, impaired endothelium-dependent  relaxation further, and aggravated inflammation (all\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05). The serum level of  8-isoprostaglandin F\n            <jats:sub>2\u03b1<\/jats:sub>\n            , a  vasoconstrictor and antinatriuretic  arachidonic acid metabolite produced by oxidative  stress, was increased 400% in GK rats on a high-sodium diet. Valsartan  decreased blood pressure in rats fed a low-sodium diet and prevented  the inflammatory response. In rats fed a high-sodium diet, valsartan  did not decrease blood pressure or improve endothelial  dysfunction but protected against albuminuria,  inflammation, and oxidative stress. As measured by quantitative  autoradiography, AT\n            <jats:sub>1<\/jats:sub>\n            receptor  expression in the medulla was decreased in GK compared with Wistar  rats, whereas cortical AT\n            <jats:sub>1<\/jats:sub>\n            receptor expression,  medullary and cortical angiotensin type 2  (AT\n            <jats:sub>2<\/jats:sub>\n            ) receptor expressions, and adrenal ACE and  neutral endopeptidase expressions were unchanged. A  high-sodium diet did not influence renal AT\n            <jats:sub>1<\/jats:sub>\n            ,  AT\n            <jats:sub>2<\/jats:sub>\n            , ACE, or neutral  endopeptidase expressions. In valsartan-treated GK  rats, the cortical and medullary AT\n            <jats:sub>1<\/jats:sub>\n            receptor  expressions were decreased in the presence and absence of a high-sodium  diet. A high-sodium diet increased plasma brain natriuretic  peptide concentrations in presence and absence of valsartan treatment.  We conclude that hypertension in GK rats is salt sensitive and  associated with endothelial dysfunction and  perivascular inflammation. AT\n            <jats:sub>1<\/jats:sub>\n            receptor blockade  ameliorates inflammation during a low-sodium diet and partially  protects against salt-induced vascular damage by blood  pressure\u2013independent  mechanisms.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.37.2.433","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:25:31Z","timestamp":1339460731000},"page":"433-439","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":124,"title":["Endothelial Dysfunction and Salt-Sensitive Hypertension in Spontaneously Diabetic Goto-Kakizaki Rats"],"prefix":"10.1161","volume":"37","author":[{"given":"Zhong Jian","family":"Cheng","sequence":"first","affiliation":[{"name":"From the Institute of Biomedicine (Z.J.C., T.V., K.N., H.V., E.M.A.M.),  Department of Pharmacology and Toxicology, University of Helsinki, Helsinki,  Finland; the Department of Medicine (I.T.), Helsinki University Central  Hospital and Minerva Institute for Medical Research, Helsinki, Finland; the  Department of Pharmacology and Toxicology (H.R., D.M., J.-K.P., F.C.L.),  University of Oulu, Oulu, Finland; and the Franz Volhard Clinic, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Vaskonen","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine (Z.J.C., T.V., K.N., H.V., E.M.A.M.),  Department of Pharmacology and Toxicology, University of Helsinki, Helsinki,  Finland; the Department of Medicine (I.T.), Helsinki University Central  Hospital and Minerva Institute for Medical Research, Helsinki, Finland; the  Department of Pharmacology and Toxicology (H.R., D.M., J.-K.P., F.C.L.),  University of Oulu, Oulu, Finland; and the Franz Volhard Clinic, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkka","family":"Tikkanen","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine (Z.J.C., T.V., K.N., H.V., E.M.A.M.),  Department of Pharmacology and Toxicology, University of Helsinki, Helsinki,  Finland; the Department of Medicine (I.T.), Helsinki University Central  Hospital and Minerva Institute for Medical Research, Helsinki, Finland; the  Department of Pharmacology and Toxicology (H.R., D.M., J.-K.P., F.C.L.),  University of Oulu, Oulu, Finland; and the Franz Volhard Clinic, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaisa","family":"Nurminen","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine (Z.J.C., T.V., K.N., H.V., E.M.A.M.),  Department of Pharmacology and Toxicology, University of Helsinki, Helsinki,  Finland; the Department of Medicine (I.T.), Helsinki University Central  Hospital and Minerva Institute for Medical Research, Helsinki, Finland; the  Department of Pharmacology and Toxicology (H.R., D.M., J.-K.P., F.C.L.),  University of Oulu, Oulu, Finland; and the Franz Volhard Clinic, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heikki","family":"Ruskoaho","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine (Z.J.C., T.V., K.N., H.V., E.M.A.M.),  Department of Pharmacology and Toxicology, University of Helsinki, Helsinki,  Finland; the Department of Medicine (I.T.), Helsinki University Central  Hospital and Minerva Institute for Medical Research, Helsinki, Finland; the  Department of Pharmacology and Toxicology (H.R., D.M., J.-K.P., F.C.L.),  University of Oulu, Oulu, Finland; and the Franz Volhard Clinic, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heikki","family":"Vapaatalo","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine (Z.J.C., T.V., K.N., H.V., E.M.A.M.),  Department of Pharmacology and Toxicology, University of Helsinki, Helsinki,  Finland; the Department of Medicine (I.T.), Helsinki University Central  Hospital and Minerva Institute for Medical Research, Helsinki, Finland; the  Department of Pharmacology and Toxicology (H.R., D.M., J.-K.P., F.C.L.),  University of Oulu, Oulu, Finland; and the Franz Volhard Clinic, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Muller","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine (Z.J.C., T.V., K.N., H.V., E.M.A.M.),  Department of Pharmacology and Toxicology, University of Helsinki, Helsinki,  Finland; the Department of Medicine (I.T.), Helsinki University Central  Hospital and Minerva Institute for Medical Research, Helsinki, Finland; the  Department of Pharmacology and Toxicology (H.R., D.M., J.-K.P., F.C.L.),  University of Oulu, Oulu, Finland; and the Franz Volhard Clinic, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon-Keun","family":"Park","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine (Z.J.C., T.V., K.N., H.V., E.M.A.M.),  Department of Pharmacology and Toxicology, University of Helsinki, Helsinki,  Finland; the Department of Medicine (I.T.), Helsinki University Central  Hospital and Minerva Institute for Medical Research, Helsinki, Finland; the  Department of Pharmacology and Toxicology (H.R., D.M., J.-K.P., F.C.L.),  University of Oulu, Oulu, Finland; and the Franz Volhard Clinic, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich C.","family":"Luft","sequence":"additional","affiliation":[{"name":"From the Institute of Biomedicine (Z.J.C., T.V., K.N., H.V., E.M.A.M.),  Department of Pharmacology and Toxicology, University of Helsinki, Helsinki,  Finland; the Department of Medicine (I.T.), Helsinki University Central  Hospital and Minerva Institute for Medical Research, Helsinki, Finland; the  Department of Pharmacology and Toxicology (H.R., D.M., J.-K.P., F.C.L.),  University of Oulu, Oulu, Finland; and the Franz Volhard Clinic, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eero M. 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