Mechanism of diminished contractile response to catecholamines during acidosis.
To examine mechanisms of diminished contractile response to catecholamines during acidosis, we studied contractile properties, beta-adrenergic receptor properties, and intracellular pH of intact, cultured myocardial cells from chick embryo ventricle at pH 7.4 and 6.8. Contractile response was measured with an optical-video system. On changing the superfusing buffer from pH 7.4 to 6.8 there was a decline in contractile amplitude to 80% of control by 20 min. Fluorimetrically determined intracellular pH declined over a similar time course from 7.11 +/- 0.05 to 6.96 +/- 0.07 (P less than 0.05). After 45 min at pH 6.8 the contractile response to 1 microM isoproterenol was less than half of the response at pH 7.4. Antagonist and agonist ligand-binding properties of the beta-adrenergic receptor were determined in the intact cells under conditions identical to those for the contractility studies. With the use of the hydrophilic antagonist [3H]CGP-12177 that selectively labels cell-surface receptors, agonist competition studies demonstrated that acidosis had no significant effect on antagonist or agonist affinity but decreased beta-receptor number from 21 +/- 3 to 11 +/- 3 fmol/mg protein (P less than 0.02). It is probable that a decline in the number of beta-receptors on the cell surface contributes to contractile hyporesponsiveness to catecholamines during acidosis.
Marsh
J D
JD
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
Margolis
T I
TI
Kim
D
D
D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo; D006863:Hydrogen-Ion Concentration; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D002395:Catecholamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; C033394:CGP 12177