REDUCED CARDIAC CONTRACTILE RESPONSIVENESS TO ISOPROTERENOL IN OBESE RABBITS

Although obesity is characterized by increased sympathetic nervous sys tem activity, there is often a paradoxical reduction in cardiovascular end-organ response to sympathetic stimulation. Mechanisms involved in reduced sympathetic responsiveness in obesity have not been well char acterized. Therefore, we determined cardiac contractile responsiveness to beta-stimulation in the obese rabbit model using both isolated hea rt (IH) and isolated papillary muscle (IPM) preparations. Female New Z ealand White rabbits were fed control (IH: n=9; IPM: n=6) or 10% fat d iets (IH: n=9; IPM: n=7) for 12 weeks. Contractile responsiveness in t he IH was determined using a modified Langendorff preparation to evalu ate the dose-response relationship between isoproterenol and 1) peak d eveloped pressure/g of left ventricular wet weight and 2) maximal rate of pressure development (+ dP/dt/P). Contractile responsiveness in th e IPM was determined using right ventricular papillary muscles to eval uate the dose-response relationship between isoproterenol and (1) peak developed tension (T)/mm(2) cross-sectional area (CSA) and (2) maxima l rate of tension development (dT/dt/CSA). In the IH, baseline and max imum developed pressure/g were reduced in obese rabbits by 37% and 31% , respectively (P less than or equal to.05). In the IPM, baseline and maximum T/CSA responses were reduced in obese rabbits by 59% and 33%, respectively (P less than or equal to.05). Potency of isoproterenol as reflected by the EC50 did not differ between lean and obese animals i n either preparation. These results demonstrate that left ventricular contractility in obesity is reduced at baseline and in response to sti mulation with isoproterenol and suggest that decreased responsiveness to beta-stimulation may be a factor in the obesity-related systolic dy sfunction.