High-salt intake augments the activity of the RhoA/ROCK pathway and reduces intracellular calcium in arteries from rats

Sandra Crestani, Robert Clinton Webb, José Eduardo Da Silva-Santos

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

BACKGROUND We investigated the influence of salt overconsumption on the functionality of the RhoA/Rho-associated kinase (ROCK) pathway and calcium regulation in arteries. METHODS 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. RESULTS 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 μ M) were tested. However, only higher concentrations of Y-27632 (10 and 50 μ M) 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. CONCLUSIONS 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.

Original languageEnglish (US)
Pages (from-to)389-399
Number of pages11
JournalAmerican journal of hypertension
Volume30
Issue number4
DOIs
StatePublished - Jan 1 2017

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Keywords

  • Blood pressure
  • Calcium sensitization
  • Calcium signaling
  • High-salt
  • Hypertension
  • Vascular dysfunction
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Internal Medicine

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