Faculty Collaboration Database

Chemokine receptor 2b inhibition provides renal protection in angiotensin II - salt hypertension. Hypertension 2007 Dec;50(6):1069-76

Date

10/17/2007

Pubmed ID

17938380

Pubmed Central ID

PMC2491337

DOI

10.1161/HYPERTENSIONAHA.107.098806

Scopus ID

2-s2.0-36448998082 (requires institutional sign-in at Scopus site)   68 Citations

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 kappaB 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 kappaB per microgram of protein), and RS102895 treatment lowered nuclear factor kappaB activity in ANG/HS hypertension (0.08+/-0.005 ng of activated nuclear factor kappaB per microgram of protein). Renal tumor necrosis factor-alpha 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-alpha 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.

Author List

Elmarakby AA, Quigley JE, Olearczyk JJ, Sridhar A, Cook AK, Inscho EW, Pollock DM, Imig JD

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Chemokine CCL2
Collagen
Cytochrome P-450 Enzyme System
Hypertension
Intercellular Adhesion Molecule-1
Kidney
Macrophages
Male
NF-kappa B
Rats
Rats, Sprague-Dawley
Receptors, CCR2
Sodium Chloride, Dietary
Tumor Necrosis Factor-alpha