Age-related changes in [3H]prazosin binding and phosphoinositide hydrolysis in rat ventricular myocardium

1. We investigated, using rats at 2, 12 and 24 months of age, the effect of aging on ventricular alpha 1-adrenoceptor responsiveness by measuring the [3H]prazosin binding, [3H]inositol phosphate formation, the cholesterol/phospholipid ratio and membrane viscosity. 2. The density of specific [3H]prazosin binding sites on membranes was significantly reduced with advanced age, and the binding affinity for [3H]prazosin was significantly increased. 3. Norepinephrine (NE)-induced formation of [3H]inositol phosphates in slices was also reduced with advanced age. However, the EC50 for NE stimulation of [3H]inositol phosphates was significantly higher when compared to those at adult ages. 4. The cholesterol content in membranes was significantly decreased with advanced age; concomitantly, a decrease in the cholesterol/phospholipid ratio was observed. The membrane viscosity as measured by using 1,6-diphenyl-1,3,5-hexatriene significantly decreased with advanced age. 5. These results suggest that the altered cholesterol/phospholipid ratio and/or the membrane viscosity during aging may account for the increase in the binding affinity for [3H]prazosin and/or the reduced responsiveness of aged ventricular myocardium to NE.