IL6 suppression provides renal protection independent of blood pressure in a murine model of salt-sensitive hypertension. Kidney Blood Press Res 2007;30(4):195-202
Date
06/19/2007Pubmed ID
17575466DOI
10.1159/000104094Scopus ID
2-s2.0-34447549006 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
Impaired cytochrome P450 epoxygenase enzyme (Cyp2c) regulation contributes to renal damage in angiotensin salt-sensitive hypertension (ANG/HS). We hypothesized that interleukin-6 null mice (IL6-/-) would improve Cyp2c regulation and reduce renal damage in hypertensive mice fed a high salt diet. Systolic blood pressure increased to a greater extent in ANG/HS hypertension as compared to angiotensin (ANG) hypertension but blood pressure did not differ between WT and IL6-/- hypertensive groups. Albuminuria, a marker for renal injury, increased significantly in ANG/HS hypertension in WT mice (5,113 +/- 1,050 mug/day) and was attenuated in the ANG/HS IL6-/- group (1,306 +/- 385 mug/day). Renal Cyp2c protein expression significantly decreased with ANG/HS hypertension in WT mice as compared to high salt alone. However, the ability to upregulate Cyp2c expression in response to a high salt diet was restored in the ANG/HS IL6 deficient hypertensive mice. Renal expression of soluble epoxide hydrolase, which inactivates protective epoxygenase metabolites, was significantly reduced in ANG/HS IL6-/- hypertensive mice compared to the ANG/HS WT group. These data suggest that IL6, while having no effect on blood pressure, impairs regulation of epoxygenase producing Cyp2c, which could contribute to the development of renal injury in angiotensin salt-sensitive hypertension.
Author List
Manhiani MM, Quigley JE, Socha MJ, Motamed K, Imig JDMESH terms used to index this publication - Major topics in bold
AnimalsBlood Pressure
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Disease Models, Animal
Hypertension
Interleukin-6
Mice
Mice, Knockout
Sodium Chloride, Dietary
