{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:52:04Z","timestamp":1790693524655,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2017,2,6]],"date-time":"2017-02-06T00:00:00Z","timestamp":1486339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>We investigated the influence of salt overconsumption on the functionality of the RhoA\/Rho-associated kinase (ROCK) pathway and calcium regulation in arteries.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The aorta and small mesenteric arteries from rats fed a chow containing 2%, 4%, or 8% NaCl were evaluated in organ baths for the activity of the RhoA\/ROCK pathway and intracellular calcium mobilization. Components of these pathways and intracellular calcium levels were also assessed in samples from 4% NaCl group.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>In arteries from animals fed regular chow, the ROCK inhibitor Y-27632 reduced the responses to phenylephrine, even when the smallest concentrations (1 and 3 \u03bcM) were tested. However, only higher concentrations of Y-27632 (10 and 50 \u03bcM) reduced phenylephrine-induced contraction in vessels from high-salt groups. Immunoblotting revealed augmented phosphorylation of the myosin phosphatase targeting subunit 1 and increased amounts of RhoA in the membrane fraction of aorta homogenates from the 4% NaCl group. Under calcium-free solution, vessels from NaCl groups presented reduced contractile responses to phenylephrine and caffeine, compared with the regular chow group. Moreover, decreased intracellular calcium at rest and after stimulation with ATP were found in aortic smooth muscle cells from 4% NaCl-fed rats, which also showed diminished levels of SERCA2 and SERCA3, but not of IP3 and ryanodine receptors, or STIM1 and Orai1 proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Arteries from rats subjected to high-salt intake are unable to properly regulate intracellular calcium levels and present augmented activity of the calcium sensitization pathway RhoA\/ROCK. These changes may precede the development of vascular diseases induced by high-salt intake.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ajh\/hpw201","type":"journal-article","created":{"date-parts":[[2017,1,30]],"date-time":"2017-01-30T13:25:10Z","timestamp":1485782710000},"page":"389-399","source":"Crossref","is-referenced-by-count":23,"title":["High-Salt Intake Augments the Activity of the RhoA\/ROCK Pathway and Reduces Intracellular Calcium in Arteries From Rats"],"prefix":"10.1093","volume":"30","author":[{"given":"Sandra","family":"Crestani","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Universidade Federal do Paran\u00e1 1 , Curitiba, Paran\u00e1 , Brazil ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Clinton","family":"Webb","sequence":"additional","affiliation":[{"name":"Department of Physiology, Augusta University 2 , Augusta, Georgia , USA ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Eduardo","family":"da Silva-Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Biology, Department of Pharmacology, Universidade Federal de Santa Catarina 3 , Florian\u00f3polis, Santa Catarina , Brazil ."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,2,6]]},"reference":[{"key":"2024020714265793200_CIT0001","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.tcm.2005.08.004","article-title":"Salt-sensitive hypertension, Na+\/Ca2+ exchanger, and vascular smooth muscle","volume":"15","author":"Iwamoto","year":"2005","journal-title":"Trends Cardiovasc Med"},{"key":"2024020714265793200_CIT0002","doi-asserted-by":"crossref","first-page":"I3","DOI":"10.1161\/01.HYP.17.1_Suppl.I3","article-title":"Observational studies of salt and blood 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novel serine\/threonine kinase, as a putative target for small GTP binding protein Rho","volume":"15","author":"Matsui","year":"1996","journal-title":"EMBO J"},{"key":"2024020714265793200_CIT0007","doi-asserted-by":"crossref","first-page":"12257","DOI":"10.1074\/jbc.272.19.12257","article-title":"Rho-associated kinase directly induces smooth muscle contraction through myosin light chain phosphorylation","volume":"272","author":"Kureishi","year":"1997","journal-title":"J Biol Chem"},{"key":"2024020714265793200_CIT0008","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1038\/40187","article-title":"Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension","volume":"389","author":"Uehata","year":"1997","journal-title":"Nature"},{"key":"2024020714265793200_CIT0009","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1161\/01.RES.0000059987.90200.44","article-title":"Activation of RhoA and inhibition of myosin phosphatase as important 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