IL6 suppression provides renal protection independent of blood pressure in a murine model of salt-sensitive hypertension.

Abstract

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.

• Authors: M M Manhiani, J E Quigley, M J Socha, K Motamed, J D Imig
• Journal: Kidney & blood pressure research (Kidney Blood Press Res) Vol. 30 Issue 4 Pg. 195-202 ( 2007) ISSN: 1423-0143 [Electronic] Switzerland
• PMID: 17575466 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright 2007 S. Karger AG, Basel.

Chemical References

• Cytochrome P-450 Enzyme Inhibitors
• Interleukin-6
• Sodium Chloride, Dietary
• cytochrome P-450 CYP2C subfamily
• Cytochrome P-450 Enzyme System

Topics

• Animals
• Blood Pressure (physiology)
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Enzyme System (metabolism)
• Disease Models, Animal
• Hypertension (chemically induced, enzymology, metabolism, prevention & control)
• Interleukin-6 (antagonists & inhibitors, biosynthesis, physiology)
• Mice
• Mice, Knockout
• Sodium Chloride, Dietary (administration & dosage, adverse effects)