Published online before print July 18, 2005, doi: 10.1161/01.HYP.0000175474.99326.bf
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(Hypertension. 2005;46:326.)
© 2005 American Heart Association, Inc.
Original Articles |
Melanocortin-4 Receptor–Deficient Mice Are Not Hypertensive or Salt-Sensitive Despite Obesity, Hyperinsulinemia, and Hyperleptinemia
From the Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson.
Correspondence to Lakshmi S. Tallam, PhD, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216-4505. E-mail ltallam{at}physiology.umsmed.edu
The purpose of this study was to test whether the melanocortin-4 receptor (MC4R) is critical in the development of hypertension associated with obesity and its metabolic disorders. MC4R-deficient homozygous (–/–) and heterozygous (+/–) and wild-type (WT) C57BL/6J mice 17 to 19 weeks old (n=5 to 7 per group) were implanted with telemetry devices for monitoring 24-hour mean arterial pressure (MAP) and heart rate (HR). After 3-day stable control measurements on normal-salt diet (NSD; 0.4% NaCl), mice received a high-salt diet (HSD; 4% NaCl) for 7 days, followed by 3-day recovery on NSD. MC4R (–/–) mice were severely obese compared with MC4R (+/–) and WT mice (body weight 48±1.5 versus 31±0.6 and 30±0.5 g respectively). On NSD, MAP was similar in all groups of mice (MC4R (–/–) 110±3 mm Hg; MC4R (+/–) 109±2 mm Hg; WT 114±2 mm Hg), and HR in MC4R (–/–) was lower than in WT (604±5 versus 645±9 bpm; P<0.05) but not different from MC4R (+/–) (625±13 bpm) mice. HSD did not significantly alter MAP or HR in any of the groups. Epididymal and retroperitoneal fat weights and plasma leptin levels were several-fold greater in MC4R (–/–) compared with MC4R (+/–) and WT mice. Plasma insulin and glucose levels were also significantly greater in MC4R (–/–) than in MC4R (+/–) and WT mice. These data suggest that despite obesity, visceral adiposity, hyperleptinemia, and hyperinsulinemia, MC4R (–/–) mice are neither hypertensive nor salt sensitive, indicating that a functional MC4R may be necessary for the development of hypertension associated with obesity and its metabolic abnormalities.
Key Words: obesity • insulin resistance • hypertension, sodium-dependent • arterial pressure • renin-angiotensin system
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