{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:53:55Z","timestamp":1773291235103,"version":"3.50.1"},"reference-count":24,"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":[[2004,4]]},"abstract":"<jats:p>Increased expression of phosphoinositide 3-kinase (PI3-kinase) mediates elevated tone in the aorta from hypertensive deoxycorticosterone acetate (DOCA)-salt rats. In this article, we hypothesized that (1) alterations observed with respect to PI3-kinase observed in the aorta would also occur in mesenteric resistance arteries responsible for determining total peripheral resistance (TPR) and (2) p110\u03b4 activity was increased and localized to vascular smooth muscle cells (VSMCs), and was responsible for the increase in spontaneous tone in aortae from DOCA-salt rats. Mesenteric resistance arteries and aorta were isolated from DOCA-salt (190\u00b13 mm Hg) and sham (121\u00b12 mm Hg) rats. Myograph experiments revealed LY294002 (20 \u03bcmol\/L), a PI3-kinase inhibitor, significantly decreased tone in mesenteric resistance arteries from DOCA-salt rats as compared with sham (\u221249\u00b112 mg versus \u221210\u00b17 mg). Western analyses of resistance artery protein homogenate revealed p85\u03b1 and p110\u03b4 subunit protein, with significantly elevated levels of p110\u03b4 protein in the DOCA-salt compared with sham rats (0.30\u00b10.07 versus 0.16\u00b10.04% smooth muscle alpha-actin arbitrary units). Immunohistochemistry revealed p110\u03b4-specific staining in VSMCs, with more intense staining in aortae from DOCA-salt rats. Compared with aortae from sham, p110\u03b4-associated PI3-kinase activity was increased in DOCA-salt (158% of sham) and likely responsible for spontaneous tone because the p110\u03b4 specific inhibitor IC87114 decreased spontaneous tone in a concentration-dependent manner. Collectively, these data further implicate the p110\u03b4 isoform of PI3-kinase in arterial hyperresponsiveness in hypertension at the level of both large and small arteries.<\/jats:p>","DOI":"10.1161\/01.hyp.0000118518.20331.e8","type":"journal-article","created":{"date-parts":[[2004,3,2]],"date-time":"2004-03-02T01:56:29Z","timestamp":1078192589000},"page":"885-890","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["PI3-Kinase Upregulation and Involvement in Spontaneous Tone in Arteries From DOCA-Salt Rats"],"prefix":"10.1161","volume":"43","author":[{"given":"Carrie A.","family":"Northcott","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (C.A.N., S.W.W.), Michigan State University, East Lansing; ICOS Corporation (J.S.H.), Bothell, Wash."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel S.","family":"Hayflick","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (C.A.N., S.W.W.), Michigan State University, East Lansing; ICOS Corporation (J.S.H.), Bothell, Wash."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie W.","family":"Watts","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (C.A.N., S.W.W.), Michigan State University, East Lansing; ICOS Corporation (J.S.H.), Bothell, Wash."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_1_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2760(98)00139-8"},{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.15.9907"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.13.8347"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.8.1439"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.113.17.2927"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.70.1.535"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000030861.13850.f1"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.5.H2144"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.91.4.1819"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.6.4.579"},{"key":"e_1_3_1_11_2","first-page":"57I","volume":"60","year":"1987","unstructured":"Hollenberg NK. 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Cancer Res. 2003; 63: 1667\u20131675.","journal-title":"Cancer Res"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(03)00163-9"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.HYP.0000118518.20331.e8","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T16:15:45Z","timestamp":1715530545000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.HYP.0000118518.20331.e8"}},"subtitle":["Is p110\u03b4 the Culprit?"],"short-title":[],"issued":{"date-parts":[[2004,4]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,4]]}},"alternative-id":["10.1161\/01.HYP.0000118518.20331.e8"],"URL":"https:\/\/doi.org\/10.1161\/01.hyp.0000118518.20331.e8","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,4]]},"assertion":[{"value":"2003-10-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-12-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}