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

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 kappa B 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 kappa B per microgram of protein), and RS102895 treatment lowered nuclear factor kappa B activity in ANG/ HS hypertension (0.08 +/- 0.005 ng of activated nuclear factor kappa B 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. (Hypertension. 2007; 50: 1069- 1076.).