EFFECT OF LONG-TERM BETA(2)-AGONIST DOSING ON HUMAN CARDIAC BETA-ADRENOCEPTOR EXPRESSION IN-VIVO - COMPARISON WITH CHANGES IN LUNG AND MONONUCLEAR LEUKOCYTE BETA-RECEPTORS

Background. Tachyphylaxis to the cardiac effects of beta-adrenoceptor stimulation after long-term beta(2)-agonist administration is well rec ognized, but the influence on global cardiac beta-adrenoceptor density has not been previously investigated in vivo, Positron emission tomog raphy (PET) has made possible the noninvasive quantification of region al receptor density, This study assesses the effect of long-term beta( 2)-agonist dosing on cardiac beta-adrenoceptors.Methods and Results, b eta-Adrenoceptors in the hearts of 29 healthy male subjects aged 35 +/ - 8 years were imaged and quantified in vivo by means of PET and compa red with the receptor density in the same subjects' lung tissue, Monon uclear leukocyte (MNL) beta-receptor density was determined in vitro b y means of a radioligand binding assay, beta-Receptor density was 8.41 +/- 2.03 pmol/gm tissue in heart, 10.81 +/- 1.91 pmol/gm tissue in lu ng, and 38.0 +/- 17.5 fmol/mg protein on MNLs. There was a weak relati onship between cardiac and pulmonary beta-receptor densities (r = 0.45 , p < 0.02) but not between cardiac and MNL receptor density, In seven subjects, the measurements were repeated after 2 weeks of albuterol t reatment (4 nag orally twice daily and 200 mu g inhaled four times dai ly in the first week, with doubling of the dose during the second week ), After the albuterol treatment, beta-receptor density fell on ave by 19% (p < 0.05) in the heart compared with 22% (p < 0.05) in the lung and 42% (p < in MNLs. Correlations were found between the percentage c hanges in receptor density in heart and lung (r = 0.98, p < 0.001) and in heart and MNLs (r = 0.99, p < 0.002), Conclusions, Two weeks of hi gh-dose albuterol results in equivalent downregulation of beta-recepto rs in vivo, both in the lung and in the heart.