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This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/R803    most recent 00187.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by do Carmo, J. M. Articles by Hall, J. E. PubMed PubMed Citation Articles by do Carmo, J. M. Articles by Hall, J. E.

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Impact of obesity on renal structure and function in the presence and absence of hypertension: evidence from melanocortin-4 receptor-deficient mice

University of Mississippi Medical Center, Jackson, Mississippi

Submitted 30 March 2009 ; accepted in final form 8 July 2009

The purpose of this study was to determine the long-term impact of obesity and related metabolic abnormalities in the absence and presence of hypertension on renal injury and salt-sensitivity of blood pressure. Markers of renal injury and blood pressure salt sensitivity were assessed in 52- to 55-wk-old normotensive melanocortin-4 receptor-deficient (MC4R–/–) mice and lean C57BL/6J wild-type (WT) mice and in 22-wk-old MC4R–/– and WT mice made hypertensive by N^G-nitro-L-arginine methyl ester (L-NAME) in the drinking water for 8 wk. Old MC4R–/– mice were 60% heavier, hyperinsulinemic, and hyperleptinemic but had similar mean arterial pressure (MAP) as WT mice (115 ± 2 and 117 ± 2 mmHg) on normal salt diet (0.4% NaCl). A high-salt diet (4.0% NaCl) for 12 days did not raise MAP in obese or lean mice [MAP: MC4R (–/–) 4 ± 2 mmHg; WT, 2 ± 1 mmHg]. Obese MC4R–/– mice had 23% greater glomerular tuft area and moderately increased GFR compared with WT mice. Bowman's space, total glomerular area, mesangial matrix, urinary albumin excretion (UAE), renal TGF-β and collagen expression were not significantly different between old MC4R–/– and WT mice. Renal lipid content was greater but renal macrophage count was markedly lower in MC4R–/– than WT mice. Mild increases in MAP during L-NAME treatment (16 mmHg) caused small, but greater, elevations in UAE, renal TGF-β content, and macrophage infiltration in MC4R–/– compared with WT mice without significant changes in glomerular structure. Thus despite long-term obesity and multiple metabolic abnormalities, MC4R–/– mice have no evidence of renal injury or salt-sensitivity of blood pressure. These observations suggest that elevations in blood pressure may be necessary for obesity and related metabolic abnormalities to cause major renal injury or that MC4R–/– mice are protected from renal injury by mechanisms that are still unclear.

metabolic syndrome; renal injury; salt sensitivity