Post‐β‐receptor defect in isolated hearts of obese‐hypertensive rabbits

Abstract

OBJECTIVE: To investigate whether there is a defect in the post‐β‐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 β‐receptor to directly stimulate adenylate cyclase, these results suggest that obesity‐hypertension is associated with a defect in post‐β‐receptor signaling pathways.