{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:26Z","timestamp":1744156826436},"reference-count":17,"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":[[2003,4]]},"abstract":"<jats:p>Phosphatidylinositol 3-kinase (PI3K) activity is increased in aortae from deoxycorticosterone (DOCA)-salt rats and enhanced PI3K activity contributes to the arterial hyperreactivity in these animals. Because PI3K activity is increased in DOCA-salt hypertension, we postulated that phosphorylation of Akt and glycogen synthase kinase 3 (GSK-3), serine threonine kinases that are downstream of PI3K, would be increased in DOCA-salt hypertension. In this study, we focused on GSK-3. Because GSK-3 activity is reduced by phosphorylation, we expected that its activity would be reduced in DOCA-salt hypertensive arteries and that reduced GSK-3 activity could contribute to enhanced adrenergic signaling and vascular smooth muscle hypertrophy that augment the heightened contractile response in DOCA-salt hypertension. Surprisingly, we observed a decrease in phosphorylation of GSK-3, indicating an increase in GSK-3 activity. To determine whether increased GSK-3 activity contributes to altered arterial reactivity in DOCA-salt animals, we measured isometric contraction to norepinephrine (NE) in the presence and absence of PI3K or GSK-3 inhibition. Addition of LY294002 (20 \u03bcmol\/L), a PI3K inhibitor, resulted in a rightward shift in response to NE and normalized the NE-induced contractions in the DOCA hypertensive vessels. SB415286, a GSK-3 inhibitor, resulted in a slight rightward shift in response to NE in the DOCA-salt vessels. Thus, enhanced GSK-3 activity modestly augments the effects of PI3K but does not appear to contribute greatly to the altered arterial reactivity in DOCA-salt hypertension.<\/jats:p>","DOI":"10.1161\/01.hyp.0000061762.58873.2f","type":"journal-article","created":{"date-parts":[[2003,4,3]],"date-time":"2003-04-03T21:25:00Z","timestamp":1049405100000},"page":"898-902","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["PI3-Kinase\u2013Induced Hyperreactivity in DOCA-Salt Hypertension Is Independent of GSK-3 Activity"],"prefix":"10.1161","volume":"41","author":[{"given":"Robert D.","family":"Loberg","sequence":"first","affiliation":[{"name":"From the Departments of Internal Medicine and Physiology, University of Michigan (R.D.L., F.C.B.), Ann Arbor, Mich; and Department of Pharmacology and Toxicology, Michigan State University (C.A.N., S.W.W.), East Lansing, Mich."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carrie A.","family":"Northcott","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine and Physiology, University of Michigan (R.D.L., F.C.B.), Ann Arbor, Mich; and Department of Pharmacology and Toxicology, Michigan State University (C.A.N., S.W.W.), East Lansing, Mich."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie W.","family":"Watts","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine and Physiology, University of Michigan (R.D.L., F.C.B.), Ann Arbor, Mich; and Department of Pharmacology and Toxicology, Michigan State University (C.A.N., S.W.W.), East Lansing, Mich."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"Frank C.","family":"Brosius","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine and Physiology, University of Michigan (R.D.L., F.C.B.), Ann Arbor, Mich; and Department of Pharmacology and Toxicology, Michigan State University (C.A.N., S.W.W.), East Lansing, Mich."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.5.H2144"},{"key":"e_1_3_2_2_2","first-page":"240","volume":"439","year":"2000","unstructured":"Yang Z, Wang J, Altura BT, Altura BM. 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