Post-beta-receptor defect in isolated hearts of obese-hypertensive rabbits.

Abstract

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