Differences inCardiovascular Responses to Isoproterenol inRelation toAgeandExercise Training inHealthy Men

Background. Cardiac aging ischaracterized bya reduced heartrateresponseto(-agonist stimulation withisoproterenol, butwhether theejection fraction andothercardiovascular responsesarereduced in humansislargely unknown. Inaddition, whether reduced(-agonist responsescan beimproved with exercise training hasnotbeendetermined inhumans. Methods andResuls. Cardiovascular responsestograded isoproterenol infusions (3.5, 7,14,and35 ng/kg/min for14minutes each) wereassessed in15older (age, 60-82years) and17young(age, 24-32years) rigorously screened healthy men. Thirteen older and11youngsubjects completed 6monthsofendurance training andwereretested. Atbaseline, theolder grouphadreduced responses toisoproterenol forheartrate (+65%older versus+92%young,p<0.001), systolic bloodpressure(+9%Y versus+24%,p<0.001), diastolic blood pressure(-12%versus-24%,p<0.05), ejection fraction (+12versus+20ejection fraction units, p<O.OOl), andcardiac output (+70%o versus+100%, p<0.001). Themean plasma isoproterenol concentrations achieved during theinfusions weremarginally higher (p=0.07) intheolder group(128±58, 227±64, 354±114, and700±125 pg/ml) thanintheyoung(79±20, 178±49, 273±79, and571±139pg/ml). Intensive training increased maximal oxygenconsumption by21%intheolder group(28.9±4.6 to35.1±3.8 ml/kg/min, p<O.OOl) andby17%intheyoung(44.5±5.1 to52.1±63ml/kg/min,p<0.001), buttraining didnotaugment any ofthecardiovascular responsestoisoproterenol ineither group.Themean plasmaisoproterenol concentrations atthefourinfusion doses wereunchanged after training inbothgroups. Conclusions. We conclude thatthere isan age-associated decline inheartrate, blood pressure,ejection fraction, andcardiac output responsesto(-adrenergic stimulation withisoproterenol inhealthy men. Altered (3-adrenergic responsesprobably contribute tothereduced cardiac responsestomaximalexercise thatalso occurwithaging. Furthermore, intensive exercise training doesnotincrease cardiac responses to(-adrenergic stimulation withisoproterenol ineither youngorolder men. Thereduced (3-adrenergic responseappearstobea primary age-associated change thatisnotcausedbydisease or inactivity. (Circulation 1992;86:504-512)