Objective: To determine whether decreased cardiac responsiveness to isoproterenol in obesity is associated with alterations in b-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 b-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 b-receptors and receptor affinity for 125 I-iodocyanopindolol. Four-parameter logistic regression was used to determine minimum, maximum, slope and EC 50 for isoproterenol-stimulated adenylyl cyclase activity. Results: Obese rabbits had elevated resting blood pressure and heart rate, and higher ventricular weights. However, badrenoceptor density and affinity were not significantly different in lean and obese rabbits. Basal and maximum isoproterenolstimulated 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. EC 50 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 b-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.

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