Relationship between adenylate cyclase activity and regional myocardial energetics in experimental left ventricular hypertrophy

Abstract

The aim of this study was to examine the responsiveness of the hypertrophied left ventricle to β-adrenergic stimulation in a pressure overload model produced by valvular aortic stenosis and characterized by reduced β-adrenoceptor number. The study was designed to correlate changes in global and regional cardiac work and energetics in response to isoproterenol with adenylate cyclase activity. Eleven anesthetized dogs with left ventricular hypertrophy and 11 controls were studied at rest and during 0.5 and 1.0 μg/kg/min isoproterenol infusion. We measured regional work from segment length and force changes with ultrasonic dimension crystals and miniature force gauges in addition to arterial and left ventricular blood pressure and cardiac output. Regional myocardial oxygen consumption was calculated from O 2 extraction using microspectrophotometry and blood flow using radioactively labeled microspheres. Adenylate cyclase activity was assayed at baseline and after stimulation with forskolin. Isoproterenol significantly increased heart rate, dP dt max , cardiac output, and external work to similar levels in control and hypertrophied animals. Similarly, regional work increased from 463 ± 115 to 995 ± 584 g × mm/min for controls and from 392 ± 156 to 1175 ± 577 for hypertrophied dogs with high dose isoproterenol. Regional O 2 consumption also increased to similar levels (20.3 ± 14.7 vs 16.2 ± 6.3 ml O 2/min/100 g) in both groups. Adenylate cyclase activity was lower in hypertrophy at baseline (23.9 ± 7.3 vs 62.9 ± 14.2 p M/min/mg protein for controls), but was the same as for controls with forskolin stimulation. The results indicate that the retained stimulated activity of adenylate cyclase compensated for the decreased β-adrenoceptor number in this model of hypertrophy thereby sustaining responsiveness to β-adrenergic stimulation.