Chemokine receptor 2b inhibition provides renal protection in angiotensin II-salt hypertension

Academic Article

Abstract

  • The present study was designed to determine whether chemokine receptor 2b (CCR2b) contributes to the development of renal injury in salt-sensitive angiotensin II (ANG) hypertension. Rats were infused with ANG and fed a high-salt diet (HS) for 14 days. Rats were divided into 4 groups: HS; HS administered the CCR2b antagonist, RS102895; Ang/HS hypertensive; and Ang/HS hypertensive administered RS102895. CCR2b inhibition slowed the progression of blood pressure elevation during the first week of ANG/HS hypertension; however, it did not alter blood pressure in the HS group. At 2 weeks, arterial pressure was not significantly different between ANG/HS and ANG/HS hypertensive rats administered RS102895. Renal cortical nuclear factor κB activity increased in ANG/HS hypertension compared with the HS group (0.11±0.006 versus 0.08±0.003 ng of activated nuclear factor κB per microgram of protein), and RS102895 treatment lowered nuclear factor κB activity in ANG/HS hypertension (0.08±0.005 ng of activated nuclear factor κB per microgram of protein). Renal tumor necrosis factor-α and intercellular adhesion molecule-1 expression increased, and Cyp2c23 expression decreased in ANG/HS hypertension compared with the HS group, and CCR2b inhibition reduced tumor necrosis factor-α and intercellular adhesion molecule-1 and increased Cyp2c23 expression. Histological immunostaining revealed increased renal monocyte and macrophage infiltration in ANG/HS hypertensive rats with decreased infiltration in rats receiving RS102895 treatment. Albuminuria and cortical collagen staining also increased in ANG/HS hypertensive rats, and RS102895 treatment lowered these effects. Afferent arteriolar autoregulatory responses to increasing renal perfusion pressure were blunted in ANG/HS hypertension, and RS102895 treatment improved this response. These data suggest that CCR2b inhibition protects the kidney in hypertension by reducing inflammation and delaying the progression of hypertension. © 2007 American Heart Association, Inc.
  • Published In

  • Hypertension  Journal
  • Digital Object Identifier (doi)

    Author List

  • Elmarakby AA; Quigley JE; Olearczyk JJ; Sridhar A; Cook AK; Inscho EW; Pollock DM; Imig JD
  • Start Page

  • 1069
  • End Page

  • 1076
  • Volume

  • 50
  • Issue

  • 6