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May 2002, Volume 26, Number 5, Pages 627-632
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Paper
bold beta-Adrenoceptor density and adenylyl cyclase activity in obese rabbit hearts
J F Carroll1,2, C K Kyser1 and M M Martin3

1Department of Integrative Physiology, University of North Texas Health Science Center, Fort Worth, TX 76107

2Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107

3Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107

Correspondence to: J F Carroll, Department of Integrative Physiology, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107-2699, USA. E-mail: jcarroll@hsc.unt.edu

Abstract

Objective: To determine whether decreased cardiac responsiveness to isoproterenol in obesity is associated with alterations in beta-receptors and/or adenylyl cyclase activity.

Animals and Design: After 12 weeks of control or ad libitum high-fat diets, left ventricular tissue from lean and obese female New Zealand white rabbits was assayed for beta-receptor binding density (11 lean, 11 obese) and isoproterenol-stimulated adenylyl cyclase activity (eight lean, 10 obese).

Measurements: Nonlinear least squares regression analysis was used to determine maximum density of beta-receptors and receptor affinity for 125I-iodocyanopindolol. Four-parameter logistic regression was used to determine minimum, maximum, slope and EC50 for isoproterenol-stimulated adenylyl cyclase activity.

Results: Obese rabbits had elevated resting blood pressure and heart rate, and higher ventricular weights. However, beta-adrenoceptor density and affinity were not significantly different in lean and obese rabbits. Basal and maximum isoproterenol-stimulated adenylyl cyclase activity did not differ between lean and obese rabbits. In addition, maximal stimulation in response to sodium flouride did not differ between lean and obese. EC50 for isoproterenol-stimulated adenylyl cyclase activity did not differ between lean and obese rabbits.

Conclusion: Obesity-related decreases in responsiveness of the isolated heart to isoproterenol are not associated with alterations in beta-receptor density and affinity. In addition, adenylyl cyclase activity appeared unchanged in ventricular preparations from obese rabbits. Decreased responsiveness to isoproterenol in obesity may be due to defects downstream of adenylyl cyclase activation of cyclic AMP.

International Journal of Obesity (2002) 26, 627-632. DOI:10.1038/sj/ijo/0801957

Keywords

obesity; cardiac beta-adrenergic signaling; cAMP; beta-receptor; adenylyl cyclase

Received 2 July 2001; revised 25 October 2001; accepted 21 November 2001
May 2002, Volume 26, Number 5, Pages 627-632
Table of contents    Previous  Abstract  Next   Full text  PDF
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