Post-beta-receptor defect in isolated hearts of obese-hypertensive rabbits.
OBJECTIVE
To investigate whether there is a defect in the post-beta-receptor signaling pathway in isolated hearts of obese, hypertensive rabbits compared with their lean, normotensive counterparts.


METHODS
Female New Zealand white rabbits were fed a maintenance (n = 5) or a 10% fat diet (n = 6) for 12 weeks.


METHODS
After 12 weeks, rabbits were weighed and resting blood pressure and heart rate measured in the conscious animal using a central ear artery catheter. The isolated heart preparation was used to measure peak developed pressure, peak rate of pressure rise (+dP/dt), and peak rate of pressure decline (-dP/dt) under control and 10(-6) M forskolin-stimulated conditions.


RESULTS
In response to forskolin, developed pressure increased 55% in lean rabbits, but only 18% in obese rabbits. Similarly, the increase in +dP/dt in response to forskolin was attenuated in obese rabbits (+52%) compared with lean rabbits (+121%). Relaxation (-dP/dt) in response to forskolin was also impaired, increasing 113% in lean rabbits but only 58% in obese rabbits.


CONCLUSIONS
Since forskolin bypasses the beta-receptor to directly stimulate adenylate cyclase, these results suggest that obesity-hypertension is associated with a defect in post-beta-receptor signaling pathways.
Carroll
J F
JF
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505, USA. jcarroll@hsc.unt.edu
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D009200:Myocardial Contraction / Q000187:drug effects; D009765:Obesity / Q000503:physiopathology*; D011817:Rabbits; D011897:Random Allocation; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015398:Signal Transduction
D002316:Cardiotonic Agents; D011943:Receptors, Adrenergic, beta; D005576:Colforsin