BACKGROUND: Tachyphylaxis to the cardiac effects of beta-adrenoceptor stimulation after long-term @entity2263 -agonist administration is well recognized, but the influence on global cardiac beta-adrenoceptor density has not been previously investigated in vivo. Positron emission tomography (PET) has made possible the noninvasive quantification of regional receptor density. This study assesses the effect of long-term @entity2263 -agonist dosing on cardiac beta-adrenoceptors. METHODS AND RESULTS: Beta-adrenoceptors in the hearts of 29 healthy male subjects aged 35 +/- 8 years were imaged and quantified in vivo by means of PET and compared with the receptor density in the same subjects' lung tissue. Mononuclear leukocyte (MNL) beta-receptor density was determined in vitro by 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 lung, and 38.0 +/- 17.5 fmol/mg protein on MNLs. There was a weak relationship 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 @entity3045 treatment (4 mg orally twice daily and 200 microg inhaled four times daily in the first week, with doubling of the dose during the second week). After the @entity3045 treatment, beta-receptor density fell on average by 19% (p < 0.05) in the heart compared with 22% (p < 0.05) in the lung and 42% (p < 0.05) in MNLs. Correlations were found between the percentage changes 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 high-dose @entity3045 results in equivalent downregulation of beta-receptors in vivo, both in the lung and in the heart.

Effect of long-term XXXX -agonist dosing on human cardiac beta-adrenoceptor expression in vivo: comparison with changes in lung and mononuclear leukocyte beta-receptors.

@entity2263 :: ('10242', 'Gene') :: ['beta2'] @entity3045 :: ('MESH:D000420', 'Chemical') :: ['albuterol']
@entity2263 :: (10242,Gene) :: ['beta2']
