Post-β-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. DESIGN: Female New Zealand white rabbits were fed a maintenance (n = 5) or a 10% fat diet (n = 6) for 12 weeks. MEASUREMENTS: 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.