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(Hypertension. 2007;50:1057.)
© 2007 American Heart Association, Inc.

Original Articles

Axl Mediates Vascular Remodeling Induced by Deoxycorticosterone Acetate–Salt Hypertension

From the Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester, NY.

Correspondence to Vyacheslav "Slava" A. Korshunov, University of Rochester, Aab Cardiovascular Research Institute, 601 Elmwood Ave, Box 679, Rochester, NY 14642. E-mail Slava_Korshunov{at}URMC.rochester.edu

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.

Key Words: Axl • mouse • hypertension • endothelial dysfunction • remodeling • apoptosis