β-Adrenoceptor density and adenylyl cyclase activity in obese rabbit hearts

Abstract

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.

Cardiac β‐adrenergic responsiveness of obese Zucker rats: The role of AMPK

“…Our observation of reduced -adrenergic responsiveness in hearts of obese rats confirms previous findings, not only in isolated rat and rabbit hearts (Carroll et al, 1997;Carroll, Kyser, & Martin, 2002;Jiang et al, 2015;Lima-Leopoldo et al, 2011), but also using cardiac membranes (Bass & Ritter, 1985;Chatelain et al, 1981;Strassheim et al, 1992), and more importantly, in vivo assessment in conscious conditions (Bunag et al, 1990;Bussey et al, 2014). In some studies, it was not possible to associate the reduced -adrenergic responsiveness of the obese heart with a downregulation of the -ARs (Carroll et al, 2002;Ernsberger, Koletsky, Baskin, & Foley, 1994;Ferron et al, 2015;Hohl et al, 1993;Minhas et al, 2005;Vileigas et al, 2016), potentially owing to differences in obese animal models and technical approaches.…”

Saturated high-fat diet-induced obesity increases adenylate cyclase of myocardial β -adrenergic system and does not compromise cardiac function

“…Other authors also did not identify modifications in cardiac β 1 ‐AR and β 2 ‐AR from ob/ob mice and obese rabbits by fat‐enriched diet (Carroll et al. ; Minhas et al. ).…”

“…Few studies have addressed the relationship between obesity and myocardial β A system, and the findings are controversial in genetic and dietary obesity model, the latter with a predominance of unsaturated fatty acids (Carroll ; Carroll et al. ; Minhas et al. ; Dincer ).…”

ACE-inhibition, but not weight reduction restores cardiomyocyte response to β-adrenergic stimulation in the metabolic syndrome

“…It remains unclear whether this attenuated response is attributable to decreased expression of β-receptors, to distal transduction pathways defects and/or to impaired Ca 2+ handling. Previous studies showed a decreased β-receptor expression/activity; however, more recent studies demonstrate impaired β-inotropy, without changes in β-adrenoceptor expression/activity [22,23]. Minhas et al showed impaired β-adrenergic response in ob/ob, due to altered PKA-activity and reversible by leptin repletion [24].…”