Axl mediates vascular remodeling induced by deoxycorticosterone acetate-salt hypertension

Vyacheslav A. Korshunov, Matthew Daul, Michael P. Massett, Bradford C. Berk

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Axl, a receptor tyrosine kinase, was recently identified as a novel candidate gene in a genetic model of salt-sensitive hypertension (Sabra rat). Our group first reported that Axl plays a significant role in vascular remodeling in response to injury. Here we investigated the role of Axl in the pathogenesis of hypertension in a deoxycorticosterone acetate (DOCA)-salt model. Hypertension was induced in Axl wild-type (Axl) mice and Axl-deficient (Axl) mice by uninephrectomy and DOCA-salt for 6 weeks. Controls were uninephrectomized and received tap water and regular chow ad libitum. DOCA-salt treatment increased systolic blood pressure by 25 mm Hg in both genotypes after 1 week. Systolic blood pressure remained significantly elevated in Axl DOCA, whereas systolic blood pressure levels in Axl DOCA mice were the same as controls at 6 weeks. DOCA-salt increased relative kidney weight and glomerular hypertrophy by 40% compared with controls in both genotypes. Consistent with levels of systolic blood pressure, endothelium-dependent vasorelaxation was impaired in Axl DOCA mice compared with Axl controls, whereas in Axl DOCA mice relaxation responses were similar to Axl controls. In addition, endothelium-independent vasorelaxation was improved in Axl DOCA mice compared with Axl DOCA mice. Nitrotyrosine and phospho-Akt immunoreactivity was significantly reduced in arteries from Axl DOCA mice compared with Axl DOCA mice. The remodeling index of the mesenteric artery (media:lumen ratio) was significantly increased in Axl DOCA mice compared with Axl DOCA mice. Finally, increased vascular apoptosis in the Axl DOCA mice suggests a likely mechanism for Axl-dependent effects on hypertension. These data strengthen the pathogenic role for Axl in salt-sensitive hypertension.

Original languageEnglish
Pages (from-to)1057-1062
Number of pages6
JournalHypertension
Volume50
Issue number6
DOIs
StatePublished - Dec 2007

Keywords

  • Apoptosis
  • Axl
  • Endothelial dysfunction
  • Hypertension
  • Mouse
  • Remodeling

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