ALTERATIONS IN THE REGIONAL BETA-ADRENERGIC SYSTEM IN EXPERIMENTAL LEFT-VENTRICULAR HYPERTROPHY

Study objective - The aim of the study was to determine the changes in the β adrenergic system induced by cardiac hypertrophy due to valvular aortic stenosis.Design - Density of β adrenoceptors, cardiac tissue noradrenalime concentrations, coronary blood flow (using radioactive microspheres), and haemodynamic variables were compared in a model of experimental aortic valve stenosis of 6 month's duration and in sham operated controls.Subjects - 14 mongrel dogs with aortic stenosis and eight sham operated litter mates were used in the studies.Measurements and results - Heart weight to body weight ratio was 33% greater in dogs with aortic valve stenosis than in controls. There were no haemodynamic differences except for a left ventricular to aortic systolic pressure gradient of 38 (SD 22) mm Hg in the aortic stenosis group. Response of left ventricular dP/dtmax to dopamine was similar in the two groups, as was coronary flow. Density of β adrenoceptors (Bmax) as measured by (125I)-iodopindolol binding was reduced in ventricles from the aortic stenosis group compared to control: 41.2(13.3) v 59.1(8.1) fmol·mg-1 protein, p<0.005. Affinity of receptor for ligand (Kd) was not affected by cardiac hypertrophy. Tissue noradrenaline concentration was reduced in the hypertrophy group: 1108(402) (control) v 438(13) ng·g-1 initial wet weight (aortic stenosis), p<0.05. There were no significant subepicardial v subendocardial differences in any variable.Conclusions - Cardiac hypertrophy induced by aortic valve stenosis over a 6 month period is accompanied by a decrease in the density of ventricular β adrenoceptors per gram and a decrease in ventricular noradrenaline concentration, though responsiveness of the whole heart is maintained.